original_index int64 2 1.77M | extracted_from_file stringclasses 489 values | date_of_experiment timestamp[ns]date | grant_date timestamp[ns]date 1976-01-01 00:01:00 2016-01-01 00:09:00 | is_mapped bool 1 class | rxn_str stringlengths 87 6.12k | reactant_000 stringlengths 1 902 | reactant_001 stringlengths 1 902 ⌀ | reactant_002 null | agent_000 stringlengths 1 540 ⌀ | agent_001 stringlengths 1 852 ⌀ | agent_002 stringlengths 1 247 ⌀ | agent_003 null | agent_004 null | agent_005 null | agent_006 null | agent_007 null | agent_008 null | agent_009 null | agent_010 null | agent_011 null | agent_012 null | agent_013 null | agent_014 null | agent_015 null | agent_016 null | solvent_000 stringclasses 446 values | solvent_001 stringclasses 405 values | solvent_002 null | solvent_003 null | solvent_004 null | solvent_005 null | solvent_006 null | solvent_007 null | solvent_008 null | solvent_009 null | solvent_010 null | temperature float64 -230 30.1k ⌀ | rxn_time float64 0 2.16k ⌀ | procedure_details stringlengths 8 24.5k | product_000 stringlengths 1 484 | product_001 null | yield_000 float64 0 90,205,156,600B ⌀ | yield_001 float64 0 100M ⌀ |
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1,719,774 | ord_dataset-3f2a531ffbae4b9eb1048afcd7953beb | null | 2016-01-01T00:04:00 | true | Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](=[O:12])[O:4][C:3]=1[CH:13]([OH:15])[CH3:14].[CH3:16][N:17]([CH3:27])[C:18]1[CH:19]=[C:20](B(O)O)[CH:21]=[CH:22][CH:23]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:16][N:17]([CH3:27])[C:18]1[CH:23]=[C:22]([C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5](=[O:12])[O:4][C:3]=2[CH:13]([OH:15])[CH3:14])[CH:21]=[CH:20][CH:19]=1 | CN(C)c1cccc(B(O)O)c1 | CC(O)c1oc(=O)c2ccccc2c1Br | null | c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1 | O=C([O-])[O-] | [Cs+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was made in a similar way as that of the intermediate B1 using 4-bromo-3-(1-hydroxyethyl)-1H-isochromen-1-one (Intermediate A2, 0.5 g, 1.86 mmol), 3-(dimethylamino)phenylboronic acid (0.46 g, 2.79 mmol), Pd(PPh3)4 (0.11 g, 0.093 mmol) and Cs2CO3 (0.78 g, 2.41 mmol) to afford the title compound (0.2 g, 35%). | CC(O)c1oc(=O)c2ccccc2c1-c1cccc(N(C)C)c1 | null | 34.8 | null |
546,191 | ord_dataset-d31180f42ced44719fd9e72685c798bf | null | 2002-01-01T00:05:00 | true | [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]([C:26]4[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=4)([C:20]4[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=4)[OH:19])[CH:16]=3)[N:11]=[C:10]([O:32]C)[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.Cl>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]([OH:19])([C:20]4[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=4)[C:26]4[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=4)[CH:16]=3)[NH:11][C:10](=[O:32])[CH:9]=2)[CH:5]=[CH:6][CH:7]=1 | COc1cc(-c2cccc(Cl)c2)c2cc(C(O)(c3cccnc3)c3cccnc3)ccc2n1 | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | null | Following the same procedure as described in example 1F, [4-(3-chloro-phenyl)-2-methoxy-quinolin-6-yl]-di-pyridin-3-yl-methanol (300 mg, 0.66 mmol) was treated with HCl in aqueous THF to yield the title compound (290 mg, 100% yield). | O=c1cc(-c2cccc(Cl)c2)c2cc(C(O)(c3cccnc3)c3cccnc3)ccc2[nH]1 | null | 99.9 | null |
742,180 | ord_dataset-437aa6654d5044ddaef3346dc4c6e08a | null | 2006-01-01T00:11:00 | true | [C:1](Cl)(=O)[C:2]([Cl:4])=[O:3].[CH3:7][O:8][C:9]1[CH:17]=[CH:16]C(C(O)=O)=[CH:11][C:10]=1[N+:18]([O-:20])=[O:19]>C1COCC1>[CH3:7][O:8][C:9]1[CH:17]=[CH:16][C:1]([C:2]([Cl:4])=[O:3])=[CH:11][C:10]=1[N+:18]([O-:20])=[O:19] | COc1ccc(C(=O)O)cc1[N+](=O)[O-] | O=C(Cl)C(=O)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | null | Oxalyl chloride (15.8 ml, 180 mmol) was added dropwise with stirring to a solution of 4-methoxy-3-nitrobenzoic acid (7.00 g, 36.00 mmol) in THF containing 10 μL DMF. After 1 h the solvent was removed under reduced pressure. The product was used directly in the next step. | COc1ccc(C(=O)Cl)cc1[N+](=O)[O-] | null | null | null |
1,112,311 | ord_dataset-375a420ee9b042918ddca20f02df37d3 | null | 2011-01-01T00:11:00 | true | [Si]([O:8][C@@H:9]([CH3:37])[C@H:10]([C:22]1[O:26][C:25]([C:27]2[CH:32]=[CH:31][C:30]([NH:33][C:34](=[O:36])[CH3:35])=[CH:29][CH:28]=2)=[N:24][N:23]=1)[NH:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]#[N:19])=[C:14]([Cl:20])[C:13]=1[CH3:21])(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:20][C:14]1[C:13]([CH3:21])=[C:12]([NH:11][C@@H:10]([C:22]2[O:26][C:25]([C:27]3[CH:28]=[CH:29][C:30]([NH:33][C:34](=[O:36])[CH3:35])=[CH:31][CH:32]=3)=[N:24][N:23]=2)[C@@H:9]([OH:8])[CH3:37])[CH:17]=[CH:16][C:15]=1[C:18]#[N:19] | CC(=O)Nc1ccc(-c2nnc([C@H](Nc3ccc(C#N)c(Cl)c3C)[C@H](C)O[Si](C)(C)C(C)(C)C)o2)cc1 | null | null | CCCC[N+](CCCC)(CCCC)CCCC | [F-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 11 | null | To a pre-cooled (−55° C.) solution of N-(4-(5-((1R,2S)-2-(tert-butyldimethylsilyloxy)-1-(3-chloro-4-cyano-2-methylphenylamino)propyl)-1,3,4-oxadiazol-2-yl)phenyl)acetamide (216 mg, 0.40 mmol) in THF (20 mL) was added TBAF (0.48 mL, 0.48 mmol, 1 M solution in THF) over 5 minutes. Upon complete addition the reaction mixture was allowed to warm to 11° C. over 3 h and quenched with sat. aq. NH4Cl (15 mL). The resulting mixture was partitioned between H2O (25 mL) and EtOAc (40 mL). The aqueous layer was extracted with EtOAc (50 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure to provide a colourless oil, which was purified by flash chromatography over silica gel (50-100% EtOAc in hexanes) to provided the title compound as a colourless solid (150 mg, 88%): 1H NMR (400 MHz, d6-acetone, δ in ppm) 9.49 (s 1H), 7.90 (dm, J=9.0 Hz, 2H), 7.80 (dm, J=9.0 Hz, 2H), 7.47 (d, J=8.8 Hz, 1H), 6.85 (d, J=8.6 Hz, 1H), 5.66 (d, J=8.4 Hz, 1H), 5.07 (dd, J=3.7, 8.4 Hz, 1H), 4.84 (br s, 1H), 4.61 (dq, J=3.5, 5.9 Hz, 1H), 2.39 (s, 3H), 2.12 (s, 3H), 1.40 (d, J=6.3 Hz, 3H). | CC(=O)Nc1ccc(-c2nnc([C@H](Nc3ccc(C#N)c(Cl)c3C)[C@H](C)O)o2)cc1 | null | 88.1 | null |
31,312 | ord_dataset-56c07ce5503b46d1805bdf471f8f1c55 | null | 1977-01-01T00:10:00 | true | [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[CH:4]=1.C([Li])CCC.CCCCCC.[CH3:22][N:23]1[C:27](=[O:28])[CH2:26][CH2:25][C:24]1=[O:29]>O1CCCC1>[CH3:22][NH:23][C:24](=[O:29])[CH2:25][CH2:26][C:27](=[O:28])[C:4]1[C:3]([O:2][CH3:1])=[CH:8][CH:7]=[CH:6][C:5]=1[O:9][CH3:10] | CN1C(=O)CCC1=O | COc1cccc(OC)c1 | null | [Li]CCCC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | CCCCCC | null | null | null | null | null | null | null | null | null | null | 8 | A solution of 1,3-dimethoxybenzene (89 ml, 0.064 mole) in dry tetrahydrofuran (480 ml) was added during 10 minutes to a stirred solution of n-butyl lithium in hexane (350 ml, 0.6 mole) under an atmosphere of nitrogen. The stirred mixture was heated under reflux for 90 minutes, then a solution of N-methyl succinimide (77 g, 0.68 mole) in dry tetrahydrofuran was added dropwise. The mixture was heated under reflux for an additional hour and then allowed to stand overnight. The supernatant was decanted and the residue was hydrolysed with 20% aqueous ammonium chloride solution (280 ml) and extracted with chloroform. The washed and dried extract was evaporated and the residue recrystallised from ethyl acetate to give N-methyl 3-(2,6-dimethoxybenzoyl)propionamide (15 g, 10%, m.p. 134°). | CNC(=O)CCC(=O)c1c(OC)cccc1OC | null | 93.3 | null |
623,987 | ord_dataset-c9f990dde2dc45d0948ecbe037a0d819 | null | 2004-01-01T00:01:00 | true | [CH3:1][O:2][C:3]1[C:12]([NH:13][C:14](=[O:22])OC2C=CC=CC=2)=[N:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1.[CH3:23][S:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1>>[CH3:1][O:2][C:3]1[C:12]([NH:13][C:14]([N:34]2[CH2:33][CH2:32][N:31]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=3[S:24][CH3:23])[CH2:36][CH2:35]2)=[O:22])=[N:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1 | COc1nc2ccccc2nc1NC(=O)Oc1ccccc1 | CSc1ccccc1N1CCNCC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Phenyl N-(2-methoxyquinoxalin-3-yl)carbamate and 1-(2-methylthiophenyl)piperazine were reacted by the same way with the example 36 to obtain the titled compound. | COc1nc2ccccc2nc1NC(=O)N1CCN(c2ccccc2SC)CC1 | null | 69.8 | null |
1,337,693 | ord_dataset-08852243bba44cb28769a5833f1515fe | null | 2013-01-01T00:09:00 | true | [CH2:1]([C:3]1[CH:4]=[C:5]([CH2:8][OH:9])[S:6][CH:7]=1)[CH3:2].[H-].[Na+].Cl[C:13]1[CH:21]2[CH:16]([CH:17]3[O:22][CH:20]2[CH2:19][CH2:18]3)[C:15](=[O:23])[CH:14]=1>C1COCC1>[CH2:1]([C:3]1[CH:4]=[C:5]([CH2:8][O:9][C:13]2[CH:21]3[CH:16]([CH:17]4[O:22][CH:20]3[CH2:19][CH2:18]4)[C:15](=[O:23])[CH:14]=2)[S:6][CH:7]=1)[CH3:2] | CCc1csc(CO)c1 | O=C1C=C(Cl)C2C3CCC(O3)C12 | null | [H-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | 25 | 3 | To a solution of (4-ethyl-thiophen-2-yl)methanol (369 mg, 2 mmol) in THF (10 ml) is added sodium hydride, 60% dispersion in mineral oil, (88 mg, 2.2 mmol) in one portion and the reaction stirred at room temp for 3 hours. The resulting dark yellow solution is then cooled to 0° C., and 5-Chloro-10-oxa-tricyclo[5.2.1.0*2,6*]dec-4-en-3-one (341 mg, 2.4 mmol) is added and the resulting brown solution allowed to warm to ambient over 30 minutes, then stirred at room temp for 17 hours. Crude reaction is purified by flash chromatography to give 5-(4-ethyl-thiophen-2-ylmethoxy)-10-oxa-tricyclo[5.2.1.0*2,6*]dec-4-en-3-one as a white solid (515 mg). | CCc1csc(COC2=CC(=O)C3C4CCC(O4)C23)c1 | null | 88.7 | null |
839,368 | ord_dataset-074f86301ec5441ab3b52d902ac06949 | null | 2008-01-01T00:09:00 | true | CO[C:3]1[CH:4]=[C:5]([CH:9]([C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH:18]=[CH:17][CH:16]=2)[CH:10]([C:13]#[N:14])[C:11]#[N:12])[CH:6]=[CH:7][CH:8]=1.[C:25]1(C)C=CC=CC=1[Mg]Br>O1CCCC1>[CH3:25][C:6]1[CH:7]=[CH:8][CH:3]=[CH:4][C:5]=1[CH:9]([C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[CH:17][CH:16]=1)[CH:10]([C:13]#[N:14])[C:11]#[N:12] | Cc1ccccc1[Mg]Br | COc1cccc(C(c2cccc3ccccc23)C(C#N)C#N)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | 1.5 | A flask was charged with (1-naphthalenylmethylene)-propanedinitrile of Example 3 (408 mg, 2 mmol) and 10 mL anhydrous tetrahydrofuran. To this stirred solution was added, at room temperature, ortho-tolyl magnesium bromide (1.2 mL, 2.4 mmol, 2 M in tetrahydrofuran). The reaction was stirred 1.5 hours, after which it was quenched with 1 N hydrochloric acid and taken up in ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, brine, dried over magnesium sulfate, filtered, and evaporated to dryness. Following purification on silica (20% ethyl acetate/hexanes) 455 mg product was isolated as an off white foam. | Cc1ccccc1C(c1cccc2ccccc12)C(C#N)C#N | null | null | null |
475,791 | ord_dataset-d56f0a7ec215495c92e641d9fa932d28 | null | 2000-01-01T00:09:00 | true | [NH2:1][C:2]1[C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[C:10]2[C:4](=[CH:5][CH:6]=[C:7]([CH2:17][C:18]([OH:20])=O)[CH:8]=[CH:9]2)[C:3]=1[C:21]([O:23][CH2:24][CH3:25])=[O:22].C([O:28][P:29]([CH2:34][O:35][NH2:36])([O:31]CC)=[O:30])C>>[NH2:1][C:2]1[C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[C:10]2[C:4](=[CH:5][CH:6]=[C:7]([CH2:17][C:18](=[O:20])[NH:36][O:35][CH2:34][P:29]([OH:31])([OH:30])=[O:28])[CH:8]=[CH:9]2)[C:3]=1[C:21]([O:23][CH2:24][CH3:25])=[O:22] | CCOC(=O)c1c2ccc(CC(=O)O)ccc-2c(C(=O)OCC)c1N | CCOP(=O)(CON)OCC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | In an analogous manner to that described in Example 26, from diethyl 2-amino-6-carboxymethyl-azulene-1,3-dicarboxylate and phosphonomethoxyamine (L. Maier, Phosphorus, Sulfur, and Silicon 1993, Vol. 76, 119-122) the title compound is obtained as an amorphous powder. | CCOC(=O)c1c2ccc(CC(=O)NOCP(=O)(O)O)ccc-2c(C(=O)OCC)c1N | null | null | null |
538,885 | ord_dataset-1884c7bf3d544afdb8d17b5d41b90a27 | null | 2002-01-01T00:03:00 | true | [NH2:1][C:2]1[CH:3]=[C:4]([CH:36]=[CH:37][C:38]=1[OH:39])[CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([CH2:12][NH:13][C:14](=[O:35])[CH2:15][NH:16][C:17](=[O:34])[C:18]2[CH:23]=[C:22]([F:24])[C:21]([F:25])=[CH:20][C:19]=2[NH:26]C(OC(C)(C)C)=O)[CH2:8][CH2:7]1.Cl>CO.O1CCOCC1>[NH2:26][C:19]1[CH:20]=[C:21]([F:25])[C:22]([F:24])=[CH:23][C:18]=1[C:17]([NH:16][CH2:15][C:14]([NH:13][CH2:12][CH:9]1[CH2:8][CH2:7][N:6]([CH2:5][C:4]2[CH:36]=[CH:37][C:38]([OH:39])=[C:2]([NH2:1])[CH:3]=2)[CH2:11][CH2:10]1)=[O:35])=[O:34] | CC(C)(C)OC(=O)Nc1cc(F)c(F)cc1C(=O)NCC(=O)NCC1CCN(Cc2ccc(O)c(N)c2)CC1 | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | C1COCCO1 | null | null | null | null | null | null | null | null | null | 25 | 8 | To a solution of 1-(3-amino-4-hydroxybenzyl)-4-[{N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl}aminomethyl]piperidine (20.0 mg, 0.035 mmol) in methanol (1 mL) was added 4 N HCl in dioxane (0.50 mL) and the solution was stirred at room temperature overnight. After the solution was concentrated, the residue was dissolved in methanol, loaded onto Varian™ SCX column, washed with CH3OH (5 mL×2), and eluted off using 2 N NH3 in CH3OH (5 mL). Concentration afforded 4-[{N-(2-amino-4,5-difluorobenzoyl)glycyl}aminomethyl]-1-(3-amino-4-hydroxybenzyl)piperidine (Compound No. 2141) (17.6 mg, quant.). The purity was determined by RPLC/MS (85%); ESI/MS m/e 448.3 (M++H, C22H27F2N5O3). | Nc1cc(CN2CCC(CNC(=O)CNC(=O)c3cc(F)c(F)cc3N)CC2)ccc1O | null | null | null |
1,148,026 | ord_dataset-b195433d5c354ddfb6cde0d53c41910f | null | 2012-01-01T00:04:00 | true | [CH2:1]([C:3]1[CH:4]=[C:5]([C:11]2[S:15][C:14]([C:16]3[S:20][C:19]([CH:21]=O)=[C:18]([CH3:23])[CH:17]=3)=[N:13][N:12]=2)[CH:6]=[C:7]([CH3:10])[C:8]=1[OH:9])[CH3:2].[CH3:24][NH:25][CH3:26]>C(O)C>[CH3:24][N:25]([CH2:21][C:19]1[S:20][C:16]([C:14]2[S:15][C:11]([C:5]3[CH:6]=[C:7]([CH3:10])[C:8]([OH:9])=[C:3]([CH2:1][CH3:2])[CH:4]=3)=[N:12][N:13]=2)=[CH:17][C:18]=1[CH3:23])[CH3:26] | CCc1cc(-c2nnc(-c3cc(C)c(C=O)s3)s2)cc(C)c1O | CNC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | null | null | The title compound (13 mg) is prepared staring from 5-[5-(3-ethyl-4-hydroxy-5-methyl-phenyl)-[1,3,4]thiadiazol-2-yl]-3-methyl-thiophene-2-carbaldehyde (21 mg, 61 μmol) and dimethylamine (33 mg, 244 μmol, as a 33% solution in ethanol) according to Method C; LC-MS: tR=0.56 min; [M+1]+=374.07; 1H NMR (D6-DMSO): δ1.18 (t, J=7.3 Hz, 3H), 2.20 (s, 3H), 2.24 (s, 6H), 2.26 (s, 3H), 2.67 (q, J=7.3 Hz, 2H), 3.57 (s, 2H), 7.47 (s, 1H), 7.56 (s, 2H). | CCc1cc(-c2nnc(-c3cc(C)c(CN(C)C)s3)s2)cc(C)c1O | null | null | null |
1,120,342 | ord_dataset-4226e9b4f9f845db967ed997270dcafc | null | 2011-01-01T00:12:00 | true | [CH2:1]1[C:6]2([CH2:11][C:10](=[O:12])[CH2:9][C:8](=[O:13])[CH2:7]2)[CH2:5][CH2:4][O:3][CH2:2]1.C1(C)C=CC=CC=1.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[CH3:33][C:34]1[C:39]([Pb+3])=[C:38]([CH3:41])[CH:37]=[C:36]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH:35]=1.Cl>CN(C)C1C=CN=CC=1.C(Cl)(Cl)Cl>[CH3:33][C:34]1[CH:35]=[C:36]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH:37]=[C:38]([CH3:41])[C:39]=1[CH:9]1[C:10](=[O:12])[CH2:11][C:6]2([CH2:5][CH2:4][O:3][CH2:2][CH2:1]2)[CH2:7][C:8]1=[O:13] | O=C1CC(=O)CC2(CCOCC2)C1 | Cc1cc(-c2ccccc2)cc(C)c1[Pb+3] | null | CC(=O)[O-] | CN(C)c1ccncc1 | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClC(Cl)Cl | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | 25 | null | To a mixture of 3-oxaspiro[5.5]undecane-8,10-dione (0.182 g, 1 mmol) and 4-dimethylamino-pyridine (0.61 g; 5 mmol) is added dry chloroform (4 ml), and the mixture is stirred under an atmosphere of nitrogen at room temperature until the solid dissolves. To this solution is then added dry toluene (2 ml), and then a solution of 3,5-dimethylbiphen-4-yllead triacetate (1.2 mmol) in chloroform is added. The reaction mixture is heated under reflux for 1 hour, then cooled to room temperature, acidified to pH=1 with 2N aqueous hydrochloric acid, filtered and the filtrate is extracted with dichloromethane (2×40 ml). The organic extracts are combined, dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated in vacuo. The residue is purified by column chromatography over silica gel to give 9-(3,5-dimethylbiphenyl-4-yl)-3-oxa-spiro[5.5]undecane-8,10-dione. | Cc1cc(-c2ccccc2)cc(C)c1C1C(=O)CC2(CCOCC2)CC1=O | null | null | null |
1,536,758 | ord_dataset-8d5c200bca27407ab9febe7598e16458 | null | 2015-01-01T00:01:00 | true | [CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:11](=[N:18][C:19]2[CH:24]=[CH:23][C:22]([Br:25])=[CH:21][CH:20]=2)[NH:12][C:13](OCC)=[O:14])[CH:10]=1)=[O:5])[CH3:2].ClCCCl>[Ti](Cl)(Cl)(Cl)Cl.C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:11]2[NH:12][C:13](=[O:14])[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([Br:25])[CH:23]=3)[N:18]=2)[CH:10]=1)=[O:5])[CH3:2] | CCOC(=O)NC(=Nc1ccc(Br)cc1)n1cc(C(=O)OCC)cn1 | null | null | Cl[Ti](Cl)(Cl)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | ClCCCl | null | null | null | null | null | null | null | null | null | 100 | 2 | Titanium (IV) chloride (2.47 mL, 22.5 mmol) was carefully added to a solution of 1-[(4-bromo-phenylimino)-ethoxycarbonylamino-methyl]-1H-pyrazole-4-carboxylic acid ethyl ester (1.84 g, 4.50 mmol) and DCE (45 mL), and the resulting solution was heated to 100° C. for 15 h. The reaction mixture was cooled to room temperature and poured into ice water (50 mL) and DCM (100 mL) was added. The biphasic mixture was stirred for 2 h, and the layers were separated. The aqueous layer was further extracted with DCM (2×50 mL). The combined organic layers were washed with brine (50 mL), dried (MgSO4), and concentrated. The residue was triturated from EtOH to yield the titled compound (1.05 g, 64% yield). MS (ESI/Cl): mass calcd. for C14H11BrN4O3, 362.0; m/z found, 363.0 [M+H]+. 1H NMR (600 MHz, DMSO-d6): 13.15 (s, 1H), 9.01 (d, J=0.5 Hz, 1H), 8.33 (s, 1H), 8.20 (d, J=2.3 Hz, 1H), 7.99 (dd, J=8.7, 2.4 Hz, 1H), 7.66 (d, J=8.8 Hz, 1H), 4.30 (q, J=7.1 Hz, 2H), 1.32 (t, J=7.1 Hz, 3H). | CCOC(=O)c1cnn(-c2nc3ccc(Br)cc3c(=O)[nH]2)c1 | null | 64.2 | null |
1,764,325 | ord_dataset-0b32b90cc77b4a3db47ad263e0bbc1a8 | null | 2016-01-01T00:09:00 | true | [NH:1]1[CH:5]=[C:4]([C:6]2[N:11]=[CH:10][C:9]3[CH:12]=[N:13][N:14]([C:15]4[N:20]=[C:19]([N:21]5[CH2:27][CH2:26][CH2:25][N:24](C(OC(C)(C)C)=O)[CH2:23][CH2:22]5)[CH:18]=[CH:17][CH:16]=4)[C:8]=3[CH:7]=2)[CH:3]=[N:2]1.Br[CH:36]1[CH2:39][CH2:38][CH2:37]1>>[N:21]1([C:19]2[N:20]=[C:15]([N:14]3[C:8]4[CH:7]=[C:6]([C:4]5[CH:5]=[N:1][N:2]([CH:36]6[CH2:39][CH2:38][CH2:37]6)[CH:3]=5)[N:11]=[CH:10][C:9]=4[CH:12]=[N:13]3)[CH:16]=[CH:17][CH:18]=2)[CH2:27][CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1 | CC(C)(C)OC(=O)N1CCCN(c2cccc(-n3ncc4cnc(-c5cn[nH]c5)cc43)n2)CC1 | BrC1CCC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Following the procedures as described in Example 61 and starting with tert-butyl 4-(6-(6-(1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-1,4-diazepane-1-carboxylate and bromocyclobutane, 147 was obtained as a yellow solid (40 mg, 35%) over two steps. 1H-NMR (500 MHz, CD3OD) δ (ppm): 9.02 (s, 1H), 8.66 (s, 1H), 8.34 (s, 1H), 8.18 (s, 1H), 7.95 (s, 1H), 7.66-7.69 (m, 1H), 7.25 (d, J=7.5 Hz, 1H), 6.59 (d, J=8.5 Hz, 1H), 4.91-4.96 (m, 1H), 3.90-3.95 (m, 4H), 3.20-3.22 (m, 2H), 3.00-3.02 (m, 2H), 2.52-2.63 (m, 4H), 2.08-2.13 (m, 2H), 1.92-1.99 (m, 2H); MS (ESI) m/z: 415 [M+H]+. | c1cc(N2CCCNCC2)nc(-n2ncc3cnc(-c4cnn(C5CCC5)c4)cc32)c1 | null | 35 | null |
1,208,361 | ord_dataset-fb72428f30234761b4216139dc228d0c | null | 2012-01-01T00:09:00 | true | [CH:1]1([C:4]([NH:6][C:7]2[N:8]=[C:9]3[CH:14]=[CH:13][C:12]([O:15][C:16]4[CH:26]=[CH:25][CH:24]=[CH:23][C:17]=4[C:18]([O:20]CC)=[O:19])=[N:11][N:10]3[CH:27]=2)=[O:5])[CH2:3][CH2:2]1.[OH-].[Na+].Cl.C(OCC)(=O)C>O1CCCC1>[CH:1]1([C:4]([NH:6][C:7]2[N:8]=[C:9]3[CH:14]=[CH:13][C:12]([O:15][C:16]4[CH:26]=[CH:25][CH:24]=[CH:23][C:17]=4[C:18]([OH:20])=[O:19])=[N:11][N:10]3[CH:27]=2)=[O:5])[CH2:3][CH2:2]1 | CCOC(=O)c1ccccc1Oc1ccc2nc(NC(=O)C3CC3)cn2n1 | null | null | Cl | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | C1CCOC1 | null | null | null | null | null | null | null | null | null | 25 | 3 | To a solution of ethyl 2-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)benzoate (200 mg, 0.54 mmol) in tetrahydrofuran (10 mL) was added 4N aqueous sodium hydroxide solution (1.5 mL), and the mixture was stirred at room temperature for 3 hr. 6N Hydrochloric acid (1.5 mL) and ethyl acetate were added to the reaction mixture, and the aqueous layer was extracted with ethyl acetate (×4). Combined organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and filtrated. The filtrate was concentrated under reduced pressure, and the residue was washed with ethyl acetate/hexane to give the title compound (130 mg, 73%) as a white solid. | O=C(O)c1ccccc1Oc1ccc2nc(NC(=O)C3CC3)cn2n1 | null | 71.2 | null |
282,818 | ord_dataset-769fac6048e548eca2d49e48f972884b | null | 1994-01-01T00:01:00 | true | [CH2:1]([C:5]1[NH:6][C:7]([C:15]#[N:16])=[C:8]([N:10]2[CH:14]=[CH:13][CH:12]=[CH:11]2)[N:9]=1)[CH2:2][CH2:3][CH3:4].CC(C)([O-])C.[K+].C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[N:30]2[C:34]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[C:41]3[CH:46]=[CH:45][C:44]([CH2:47]Br)=[CH:43][CH:42]=3)=[N:33][N:32]=[N:31]2)C=CC=CC=1>O1CCCC1>[CH2:1]([C:5]1[N:6]([CH2:47][C:44]2[CH:45]=[CH:46][C:41]([C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=3[C:34]3[NH:30][N:31]=[N:32][N:33]=3)=[CH:42][CH:43]=2)[C:7]([C:15]#[N:16])=[C:8]([N:10]2[CH:11]=[CH:12][CH:13]=[CH:14]2)[N:9]=1)[CH2:2][CH2:3][CH3:4] | BrCc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1 | CCCCc1nc(-n2cccc2)c(C#N)[nH]1 | null | CC(C)(C)[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | 0.08 | A solution of 2-butyl-5-cyano-4-(1H-pyrrol-1-yl)imidazole (Example 8, 1.7 g) in anhydrous tetrahydrofuran (20 mL) was treated with a solution of potassium tert-butoxide (0.97 g) in anhydrous tetrahydrofuran (20 mL) at room temperature. The mixture was stirred for 5 minutes then a solution of N-triphenylmethyl-5-[4'-(bromomethyl)biphenyl-2-yl]tetrazole (Example 12, 6.0 g) in anhydrous tetrahydrofuran (20 mL) was added. The reaction was stirred at room temperature under nitrogen atmosphere for 18 hours. The resulting suspension was filtered and the filtrate was evaporated. The residue was purified by flash chromatography on silica gel, eluting with chloroform hexane (90:10) to give the title compound in its triphenylmethyl-protected form. The triphenylmethyl protecting group was removed by refluxing in methanol for 24 hours. Evaporation gave a residue that was purified by chromatography on silica gel, eluting with a gradient of ethyl acetate-hexane (50:50) to ethyl acetate. Evaporation of solvents gave a gum that was redissolved in dichloromethane and evaporated to give the title compound as a solid foam. MS (FAB, thioglycerol) 470 (m+Na-1), 448 (m). | CCCCc1nc(-n2cccc2)c(C#N)n1Cc1ccc(-c2ccccc2-c2nnn[nH]2)cc1 | null | null | null |
205,505 | ord_dataset-72fffaae67c8473fb9d951cb1b026646 | null | 1990-01-01T00:03:00 | true | [OH:1][C:2]1[CH:9]=[CH:8][C:7]([C:10]([CH3:13])([CH3:12])[CH3:11])=[C:6]([Cl:14])[C:3]=1[CH:4]=[O:5].[Br:15]N1C(=O)CCC1=O.O>C(Cl)Cl>[OH:1][C:2]1[C:9]([Br:15])=[CH:8][C:7]([C:10]([CH3:11])([CH3:13])[CH3:12])=[C:6]([Cl:14])[C:3]=1[CH:4]=[O:5] | CC(C)(C)c1ccc(O)c(C=O)c1Cl | O=C1CCC(=O)N1Br | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | ClCCl | null | null | null | null | null | null | null | null | null | null | null | A solution of 1.97 g (9.26 mmol) of 2-hydroxy-5-(1,1-dimethylethyl)-6-chlorobenzaldehyde and 1.98 g (11.1 mmol) of N-bromosuccinimide in 30 ml of methylene chloride was stirred for 2 hours. Water (50 ml) was added. The organic phase was dried and evaporated. The residue was chromatographed on 150 g of silica gel eluted with 1:99 (v/v) ether:hexane. There was obtained 2.69 g (9.22 mmol, 99%) of 2-hydroxy-3-bromo-5-(1,1-dimethylethyl)-6-chlorobenzaldehyde as a white solid after recrystallization from hexane; mp 103°-105° C. | CC(C)(C)c1cc(Br)c(O)c(C=O)c1Cl | null | 99.6 | null |
1,023,881 | ord_dataset-136cfada6ce247b4919085a57363459e | null | 2011-01-01T00:01:00 | true | [CH2:1]([O:3][C:4]([C:6]1([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1)=[O:5])[CH3:2].[N:19]([O-])=[O:20].[Na+].C(O)(=O)C.C(=O)([O-])O.[Na+]>O>[CH2:1]([O:3][C:4]([C:6]1([CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:7][CH2:8][N:9]([N:19]=[O:20])[CH2:10][CH2:11]1)=[O:5])[CH3:2] | O=N[O-] | CCOC(=O)C1(Cc2ccccc2)CCNCC1 | null | O=C([O-])O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CC(=O)O | null | null | null | null | null | null | null | null | null | 25 | 8 | To a solution of 4-ethoxycarbonyl-4-benzylpiperidine (495 mg) in water (5 mL) was added sodium nitrite (276 mg) and acetic acid (201 μL) and the mixture was stirred at room temperature overnight. To the reaction mixture was added an aqueous saturated sodium hydrogencarbonate solution and the mixture was stirred and extracted with chloroform. The extract was concentrated in vacuo and the resultant crude product was purified by column chromatography on silica gel (solvent: hexane/ethyl acetate=85/15 to 80/20) and dried in vacuo to give 4-ethoxycarbonyl-4-benzyl-1-nitrosopiperidine (565 mg, yield: 100%) as a colorless solid. To a solution of the product (565 mg) in methanol (3 mL) was added zinc powder (654 mg) and then added acetic acid (3 mL) under ice-cooling and the mixture was stirred at room temperature for 3 hours. The reaction mixture was filtered and the filtrate was concentrated in vacuo. To the residue was added an aqueous saturated sodium hydrogencarbonate solution and chloroform and the mixture was stirred and extracted with chloroform. The extract was dried over magnesium sulfate and filtered. The filtrate was concentrated in vacuo to give 1-amino-4-benzyl-4-ethoxycarbonylpiperidine (508 mg, yield: 97%) as a colorless viscidity. | CCOC(=O)C1(Cc2ccccc2)CCN(N=O)CC1 | null | 102.2 | null |
218,343 | ord_dataset-640d007e35e243a286c8b7dd2b77ac1b | null | 1990-01-01T00:11:00 | true | CS(C)=O.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[CH:13](Br)([CH2:15][CH3:16])[CH3:14].[OH:18][C:19]1[C:28]([OH:29])=[C:27]2[C:22]([C:23](=[O:32])[CH2:24][C:25]([CH3:31])([CH3:30])[O:26]2)=[CH:21][CH:20]=1>COCCOCCOC>[CH:13]([O:18][C:19]1[C:28]([OH:29])=[C:27]2[C:22]([C:23](=[O:32])[CH2:24][C:25]([CH3:30])([CH3:31])[O:26]2)=[CH:21][CH:20]=1)([CH2:15][CH3:16])[CH3:14] | CC1(C)CC(=O)c2ccc(O)c(O)c2O1 | CCC(C)Br | null | O=C([O-])[O-] | [I-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | COCCOCCOC | CS(C)=O | null | null | null | null | null | null | null | null | null | 100 | 2 | In 80 ml of dimethyl sulfoxide 4.2 g (20 millimoles) of 7.8-dihydroxy-2,2-dimethyl-4-chromanone are dissolved, whereupon 10 ml of diethylene glycol dimethylether, 4.1 g (30 millimoles) of potassium carbonate, 0.5 g of potassium iodide and 3.3 (2.6 ml, 24 millimoles) of sec. butyl bromide are added. The reaction mixture is heated at 100° C. for 10 hours, poured onto 200 ml of crushed ice and extracted with 100 ml of carbon tetrachloride. To the aqueous phase 20 ml of 10% sodium hydroxide solution are added, the mixture is cooled to 0° C., acidified with concentrated hydrochloric acid and stirred at 0° C. for 2 hours. The product is filtered, washed twice with 20 ml of water, dried and crystallized from 20% ethanol. Thus 4.4. g of the desired compound are obtained, yield 83%, mp.: 108°-110° C. | CCC(C)Oc1ccc2c(c1O)OC(C)(C)CC2=O | null | 83 | null |
856,058 | ord_dataset-faa0236be76c4501841c954527cd1b6c | null | 2008-01-01T00:12:00 | true | [CH3:1][N:2]1[CH:6]=[CH:5][C:4]([C:7]([OH:9])=O)=[N:3]1.Cl.Cl.[F:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][C:22]=1[F:23])[N:19]=[C:18]([NH:24][CH2:25][CH2:26][NH:27][CH3:28])[CH:17]=[N:16]2>>[F:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][C:22]=1[F:23])[N:19]=[C:18]([NH:24][CH2:25][CH2:26][N:27]([CH3:28])[C:7]([C:4]1[C:5]([C:20]3[CH:15]=[CH:14][C:13]([F:12])=[CH:22][CH:21]=3)=[CH:6][N:2]([CH3:1])[N:3]=1)=[O:9])[CH:17]=[N:16]2 | Cn1ccc(C(=O)O)n1 | CNCCNc1cnc2cc(F)c(F)cc2n1 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared from 4-4-fluoro-phenyl)-1-methyl-1H-pyrazole-3-carboxylic acid (46 mg, 0.21 mmol) and N-(6,7-difluoro-quinoxalin-2-yl)-N′-methyl-ethane-1,2-diamine.dihydrochloride, D2 (65 mg, 0.21 mmol) according to the procedure described for Example 1, as a yellow solid (65 mg, 71%). | CN(CCNc1cnc2cc(F)c(F)cc2n1)C(=O)c1nn(C)cc1-c1ccc(F)cc1 | null | null | null |
1,176,331 | ord_dataset-0f9d2dbe929a45c3892ae75e81e99443 | null | 2012-01-01T00:06:00 | true | Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([NH2:11])=[N:9][N:10]=2)[N:7]=1.[O-:12][CH2:13][CH3:14].[Na+].O>C(O)C>[CH2:13]([O:12][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([NH2:11])=[N:9][N:10]=2)[N:7]=1)[CH3:14] | CC[O-] | Nc1nnc2ccc(Cl)nn12 | null | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | O | null | null | null | null | null | null | null | null | null | 55 | 2 | 6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-ylamine (W2.001a, 616 mg) was dissolved in absolute ethanol (40 ml) and admixed with portions of solid sodium ethoxide (990 mg). After stirring at 55° C. for 2 h, water was added and the aqueous phase was extracted three times with dichloromethane. The combined extracts were dried over sodium sulfate, filtered and concentrated. 709 mg of crude product of the desired compound were obtained in sufficient purity. | CCOc1ccc2nnc(N)n2n1 | null | 108.9 | null |
1,574,571 | ord_dataset-9741bb5fd93044078df2a45f45733054 | null | 2015-01-01T00:04:00 | true | [CH3:1][S:2]([N:5]1[CH2:10][CH:9]=[C:8]([C:11]2[CH:12]=[C:13]3[CH:19]=[C:18]([CH:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)[O:17][C:14]3=[CH:15][N:16]=2)[CH2:7][CH2:6]1)(=[O:4])=[O:3].Cl[C:27]1[N:32]=[CH:31][C:30]([Cl:33])=[CH:29][N:28]=1>>[Cl:33][C:30]1[CH:29]=[N:28][C:27]([N:23]2[CH2:24][CH2:25][CH:20]([C:18]3[O:17][C:14]4=[CH:15][N:16]=[C:11]([C:8]5[CH2:9][CH2:10][N:5]([S:2]([CH3:1])(=[O:3])=[O:4])[CH2:6][CH:7]=5)[CH:12]=[C:13]4[CH:19]=3)[CH2:21][CH2:22]2)=[N:32][CH:31]=1 | Clc1cnc(Cl)nc1 | CS(=O)(=O)N1CC=C(c2cc3cc(C4CCNCC4)oc3cn2)CC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound is prepared from 5-(1-methanesulfonyl-1,2,3,6-tetrahydro-pyridin-4-yl)-2-piperidin-4-yl-furo[2,3-c]pyridine and 2,5-dichloropyrimidine following a procedure analogous to that described for Example 23. LC (method 1): tR=1.07 min; Mass spectrum (ESI+): m/z=474/476 (Cl) [M+H]+. | CS(=O)(=O)N1CC=C(c2cc3cc(C4CCN(c5ncc(Cl)cn5)CC4)oc3cn2)CC1 | null | null | null |
1,749,904 | ord_dataset-60a3e71da3174666a50a61dcfa611a9f | null | 2016-01-01T00:07:00 | true | C(OC([NH:8][CH2:9][C:10]([O:12][CH2:13][N:14]1[C:18]2=[N:19][CH:20]=[C:21]([C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=3)[CH:22]=[C:17]2[C:16]([C:30](=[O:46])[C:31]2[C:36]([F:37])=[CH:35][CH:34]=[C:33]([NH:38][S:39]([CH2:42][CH2:43][CH3:44])(=[O:41])=[O:40])[C:32]=2[F:45])=[CH:15]1)=[O:11])=O)(C)(C)C.Cl>CCOC(C)=O>[ClH:29].[NH2:8][CH2:9][C:10]([O:12][CH2:13][N:14]1[C:18]2=[N:19][CH:20]=[C:21]([C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=3)[CH:22]=[C:17]2[C:16]([C:30](=[O:46])[C:31]2[C:36]([F:37])=[CH:35][CH:34]=[C:33]([NH:38][S:39]([CH2:42][CH2:43][CH3:44])(=[O:40])=[O:41])[C:32]=2[F:45])=[CH:15]1)=[O:11] | CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2cn(COC(=O)CNC(=O)OC(C)(C)C)c3ncc(-c4ccc(Cl)cc4)cc23)c1F | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared according to the procedure as described in Example 17 Step 3 using (5-(4-chlorophenyl)-3-(2,6-difluoro-3-(propylsulfonamido)benzoyl)-1H-pyrrolo[2,3-b]pyridin-1-yl)methyl 2-((tert-butoxycarbonyl)amino)acetate (46 mg, 0.07 mmol) and a saturated solution of HCl in EtOAc (2 mL). The title compound was obtained as a white solid (36 mg, 83.7%). The title compound was characterized by LC-MS and 1H NMR as shown below: | CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2cn(COC(=O)CN)c3ncc(-c4ccc(Cl)cc4)cc23)c1F | null | null | null |
305,003 | ord_dataset-180e296d6d6245638d4d22a59120ea01 | null | 1995-01-01T00:02:00 | true | [CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[C:18]([C:23]#[N:24])=[N:19][CH:20]=[N:21][CH:22]=3)=[CH:13][CH:12]=2)[C:8]2[C:25]([C:29]([O:31][CH3:32])=[O:30])=[CH:26][CH:27]=[CH:28][C:7]=2[N:6]=1)[CH2:2][CH2:3][CH3:4].C[Sn]([N:37]=[N+:38]=[N-:39])(C)C>C1(C)C=CC=CC=1>[CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[C:18]([C:23]4[NH:39][N:38]=[N:37][N:24]=4)=[N:19][CH:20]=[N:21][CH:22]=3)=[CH:13][CH:12]=2)[C:8]2[C:25]([C:29]([O:31][CH3:32])=[O:30])=[CH:26][CH:27]=[CH:28][C:7]=2[N:6]=1)[CH2:2][CH2:3][CH3:4] | C[Sn](C)(C)N=[N+]=[N-] | CCCCc1nc2cccc(C(=O)OC)c2n1Cc1ccc(-c2cncnc2C#N)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | A solution of methyl 2-butyl-1-[p-(4-cyanopyrimidin-5-yl)benzyl]benzimidazole-7-carboxylate (0.18 g, 0.4 mmol) and trimethyltin azide (0.27 g, 1.3 mmol) in toluene (5 ml) was heated under reflux for 28 hours. After removal of the solvent by evaporation, the residue was purified by column chromatography on silica gel. Recrystallization from ethyl acetate-isopropyl ether afforded colorless powders (40 mg, 20%), m.p. 215°-220° C. | CCCCc1nc2cccc(C(=O)OC)c2n1Cc1ccc(-c2cncnc2-c2nnn[nH]2)cc1 | null | null | null |
1,447,833 | ord_dataset-a86112d52cd54525a5e36d41f18aced2 | null | 2014-01-01T00:07:00 | true | [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH3:25])[CH2:9][C:10]([C:12]2[CH:13]=[CH:14][C:15](=[O:18])[NH:16][CH:17]=2)=[O:11])=[CH:4][CH:3]=1.IC.[C:28](=O)([O-])[O-].[K+].[K+]>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:8]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH3:25])[CH2:9][C:10]([C:12]2[CH:13]=[CH:14][C:15](=[O:18])[N:16]([CH3:28])[CH:17]=2)=[O:11])=[CH:6][CH:7]=1 | O=C([O-])[O-] | Cc1ccccc1[C@H](CC(=O)c1ccc(=O)[nH]c1)c1ccc(Br)cc1 | null | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CI | null | null | null | null | null | null | null | null | null | null | null | null | In analogy to example 161, step 1, 5-[(R)-3-(4-bromo-phenyl)-3-o-tolyl-propionyl]-1H-pyridin-2-one was reacted with iodomethane in the presence of potassium carbonate to give the title compound as a colorless solid, MS (ESI+): m/z=410.2 [M+H]+. | Cc1ccccc1[C@H](CC(=O)c1ccc(=O)n(C)c1)c1ccc(Br)cc1 | null | null | null |
1,629,968 | ord_dataset-f0794d5ded7a4d3fab45cc3d7a89ee3d | null | 2015-01-01T00:09:00 | true | [C:1]([O:5][C:6]([NH:8][C@@H:9]1[C@H:14]([OH:15])[CH2:13][CH2:12][N:11](C(OCC2C=CC=CC=2)=O)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(O)C.[Pd]>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]1[C@H:14]([OH:15])[CH2:13][CH2:12][NH:11][CH2:10]1)([CH3:4])([CH3:2])[CH3:3] | CC(C)(C)OC(=O)N[C@H]1CN(C(=O)OCc2ccccc2)CC[C@H]1O | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | null | 8 | A solution of (3S,4R)-benzyl 3-((tert-butoxycarbonyl)amino)-4-hydroxypiperidine-1-carboxylate (1.94 g, 5.54 mmol) in ethanol (48 mL) was added to a hydrogenation flask containing 10% Pd/C (0.059 g, 0.554 mmol) that had been evacuated and back-filled with N2 (×3). The flask was again evacuated and then back-filled with H2 (×3). Enough H2 to allow complete reaction was then introduced to a burette and the system closed and the flask allowed to stir under a H2 atmosphere overnight. The reaction mixture was filtered through Celite and washed with EtOH (2×20 mL) and ethyl acetate (2×20 mL). The combined filtrate was concentrated in vacuo to afford the product as a cream oily solid—tert-butyl((3S,4R)-4-hydroxypiperidin-3-yl)carbamate (1.13 g, 5.22 mmol, 94% yield). | CC(C)(C)OC(=O)N[C@H]1CNCC[C@H]1O | null | 94.2 | null |
1,610,445 | ord_dataset-9cecb3a8d3b9494191b28dcefea66af2 | null | 2015-01-01T00:07:00 | true | [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[NH:6][C:5](=[O:10])[C:4]=1[CH2:11][NH:12][C:13]([C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:17]([CH:24]([CH:26]2[CH2:31][CH2:30][CH2:29][NH:28][CH2:27]2)[CH3:25])[C:16]=1[CH3:32])=[O:14].C(N(CC)CC)C.[CH3:40][S:41](Cl)(=[O:43])=[O:42]>ClCCl>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[NH:6][C:5](=[O:10])[C:4]=1[CH2:11][NH:12][C:13]([C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:17]([CH:24]([CH:26]2[CH2:31][CH2:30][CH2:29][N:28]([S:41]([CH3:40])(=[O:43])=[O:42])[CH2:27]2)[CH3:25])[C:16]=1[CH3:32])=[O:14] | COc1cc(C)[nH]c(=O)c1CNC(=O)c1c(C)n(C(C)C2CCCNC2)c2ccccc12 | CS(=O)(=O)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | ClCCl | null | null | null | null | null | null | null | null | null | 25 | 12 | To a solution of N-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(piperidin-3-yl)ethyl)-1H-indole-3-carboxamide (20 mg, 45.81 mol) in dichloromethane (3 mL) was added triethylamine (9.27 mg, 91.63 μmol) and methanesulfonyl chloride (7.87 mg, 68.72 μmol). The mixture was stirred at room temperature for 12 hours. The mixture was evaporated and purified by preparative-HPLC (Instrument: Gilson GX281 Column: Phenomenex Gemini C18 250*21.2 mm Mobile phase A: water with 0.01 mol/1NH4HCO3; Mobile phase B: MeCN Column temperature: 30° C. Gradient: 23-53% B 10 min) to afford the title compound (7 mg, yield: 29.69%). LRMS (M+H+) m/z: calc'd 515.22. found 515.2. 1H NMR (400 MHz, METHANOL-d4) δ 0.94-1.12 (m, 2 H) 1.39 (br. S., 2 H) 1.57-1.70 (m, 4 H) 2.33 (s, 3 H) 2.63 (s, 3 H) 2.83 (d, J=9.54 Hz, 2 H) 2.88 (s, 3 H) 3.48 (br. S., 1 H) 3.79-3.87 (m, 1 H) 3.95 (s, 3 H) 4.38 (br. S., 1 H) 4.54 (s, 2 H) 6.28 (s, 1 H) 7.07-7.17 (m, 2 H) 7.58 (d, J=8.03 Hz, 1 H) 7.72 (d, J=7.53 Hz, 1 H). | COc1cc(C)[nH]c(=O)c1CNC(=O)c1c(C)n(C(C)C2CCCN(S(C)(=O)=O)C2)c2ccccc12 | null | 19.8 | null |
1,626,927 | ord_dataset-f0794d5ded7a4d3fab45cc3d7a89ee3d | null | 2015-01-01T00:09:00 | true | [CH2:1]([NH2:4])[C:2]#[CH:3].[CH2:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:8][CH2:7][C:6]1=O>C(O)C>[CH:3]1[C:10]2[C:9]3[CH:8]=[CH:7][CH:6]=[CH:5][C:14]=3[CH2:13][CH2:12][C:11]=2[N:4]=[CH:1][CH:2]=1 | O=C1CCc2ccccc2C1 | C#CCN | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | 25 | 0.25 | Propargylamine (5 mL) is added to a flask charged with a stir bar, 2-tetralone (10.00 g), NaAuCl4*2H2O (0.65 g), and ethanol (50 mL) (caution: a very exothermic reaction may evolve afterwards→keep an ice bath at hand). The resulting mixture is stirred at room temperature for 15 min and then at reflux temperature for 1 h. After cooling the mixture to room temperature, the solvent is evaporated and the residue is chromatographed on silica gel (cyclohexane/ethyl acetate 60:40) to afford the title compound as an oil. Yield: 6.78 g (56% of theory); LC (method 1): tR=1.81 min; Mass spectrum (ESI+): m/z=182 [M+H]+. Alternatively, the reaction may be conducted in a microwave oven heating with microwave irradiation to 100° C. for 10 min. | c1ccc2c(c1)CCc1ncccc1-2 | null | null | null |
583,595 | ord_dataset-60f3171f0342452f8814e7f294e2be8b | null | 2003-01-01T00:02:00 | true | Br/[C:2](/[CH3:8])=[CH:3]\[C:4]([O:6][CH3:7])=[O:5].[CH2:9]([NH:16][CH2:17][CH2:18][NH:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C1(C)C=CC=CC=1.C(N(CC)CC)C>[CH2:9]([N:16]1[CH2:17][CH2:18][N:19]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:8][CH:2]1[CH2:3][C:4]([O:6][CH3:7])=[O:5])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1 | COC(=O)/C=C(/C)Br | c1ccc(CNCCNCc2ccccc2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCN(CC)CC | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | 25 | 24 | In toluene (250 ml), N,N′-dibenzylethylenediamine (12 ml) and triethylamine (12 ml) were dissolved, followed by the dropwise addition of methyl 3-bromocrotonate (7.0 ml) under ice cooling. The resulting mixture was stirred at room temperature for 24 hours. After the addition of triethylamine (2.0 ml), the resulting mixture was stirred at room temperature for 71 hours. The insoluble matter was filtered off and the filtrate was distilled under reduced pressure. The residue was added with 10% hydrochloric acid (300 ml) and crystals so precipitated were removed by filtration. Ethyl acetate was added to the filtrate. Potassium carbonate was added to the water layer so separated to make it alkaline. Ethyl acetate was added to the resulting mixture. The organic layer so separated was washed with saturated saline and dried over anhydrous potassium carbonate. The solvent was then distilled off under reduced pressure. The residue was purified by chromatography on a silica gel column (hexane:ethyl acetate=4:1), whereby the title compound (1.07 g, 62%) was obtained. | COC(=O)CC1CN(Cc2ccccc2)CCN1Cc1ccccc1 | null | null | null |
381,122 | ord_dataset-993feac5ecf54388aa6326a220e46db3 | null | 1997-01-01T00:10:00 | true | [CH:1]1[C:17]2[C:16](C(O)=O)=[C:15]3[C:7](=[C:8]4[C:13](=[N:14]3)[CH:12]=[CH:11][CH:10]=[CH:9]4)[NH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1>C1(OC2C=CC=CC=2)C=CC=CC=1>[CH:1]1[C:17]2[CH:16]=[C:15]3[C:7](=[C:8]4[C:13](=[N:14]3)[CH:12]=[CH:11][CH:10]=[CH:9]4)[NH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1 | O=C(O)c1c2nc3ccccc3c-2[nH]c2ccccc12 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccc(Oc2ccccc2)cc1 | null | null | null | null | null | null | null | null | null | null | 30 | null | A mixture of quindoline-11-carboxylic acid prepared in Example 1 (29.2 g, 0.111 mol) and diphenylether (300 mL) was refluxed for 6 hours, cooled to 30° C. and diluted with petroleum ether (250 mL). The precipitate which formed was filtered and washed with petroleum ether thoroughly, yielding 22.1 g (90.9%) of the title compound. A portion of this material was further purified by LPLC (ethyl acetate-hexane 1:3), mp 249°-251° C. [lit 251°-252° C. (Degutis, Y. A.; Ezyarskaite, A. B. Khim. Geterotsik. Soedin. 1986, 1375)]; 1H NMR (DMSO-d6) δ 11.43 (s, 1H, NH), 8.36 (d, J=7.8, 1H), 8.29 (s, 1H), 8.19 (d, J=8.4, 1H), 8.10 (d, J=8.2, 1H), 7.67-7.53 (m, 4H), 7.27 (t, J=7.4, 1H); 13C NMR (DMSO-d6) δ 145.72, 144.03, 143.39, 132.44, 129.68, 128.68, 127.48, 126.71, 126.01, 124.84, 121.34, 120.97, 119.33, 112.99, 111.49; MS (EI, m/z) 218.1 (M+). | c1ccc2[nH]c3c4ccccc4nc-3cc2c1 | null | 91.2 | null |
960,129 | ord_dataset-ed65749688da45af8a8432967b017729 | null | 2010-01-01T00:05:00 | true | Br[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[CH2:11][C:10]2[CH:12]=[C:13]([F:16])[CH:14]=[CH:15][C:9]=2[N:8]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[F:23])[S:7]1(=[O:25])=[O:24].[CH3:26][NH2:27].Cl>>[F:16][C:13]1[CH:14]=[CH:15][C:9]2[N:8]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[F:23])[S:7](=[O:25])(=[O:24])[N:6]([CH2:5][CH2:4][CH2:3][CH2:2][NH:27][CH3:26])[CH2:11][C:10]=2[CH:12]=1 | O=S1(=O)N(CCCCBr)Cc2cc(F)ccc2N1c1ccccc1F | CN | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | In an analogous manner to Example 11 step 5, 3-(4-bromobutyl)-6-fluoro-1-(2-fluorophenyl)-3,4-dihydro-1H-2,1,3-benzothiadiazine 2,2-dioxide (0.11 g, 0.25 mmol) was reacted to methylamine and then treated with HCl to provide 4-[6-fluoro-1-(2-fluorophenyl)-2,2-dioxido-1,4-dihydro-3H-2,1,3-benzothiadiazin-3-yl]-N-methylbutan-1-amine (0.085 g, 81%) as a white solid: | CNCCCCN1Cc2cc(F)ccc2N(c2ccccc2F)S1(=O)=O | null | 81 | null |
1,479,023 | ord_dataset-c3c1091f873b4f40827973a6f1f9b685 | null | 2014-01-01T00:09:00 | true | [CH:1]1[C:6]2[C:7]3[C:18](=[O:19])[C:17]4[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=4[C:8]=3[O:9][C:10](=O)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[NH2:20][NH2:21]>C(Cl)(Cl)Cl>[NH2:20][N:21]1[C:8]2[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=3[C:18](=[O:19])[C:7]=2[C:6]2[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=2)[C:10]1=[O:9] | O=C1c2ccccc2-c2oc(=O)c3ccccc3c21 | NN | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClC(Cl)Cl | null | null | null | null | null | null | null | null | null | null | 25 | null | Benz[d]indeno[1,2-b]pyran-5,11-dione (4d) (0.150 g, 0.604 mmol) was treated with hydrazine (0.255 g, 7.964 mmol) in CHCl3 (50 mL) and the reaction mixture was heated at reflux for 16 h. The reaction mixture was allowed to cool to room temperature, diluted with CHCl3 (150 mL), and washed with sat NaHCO3 (2×50 mL). The solution was dried over sodium sulfate and concentrated to provide a red-orange solid (0.120 g, 76%): mp 272-274° C. IR (film) 3448, 3305, 1686, 1663, 1610, 1507, 1312, 762 cm−1; 1H NMR (CDCl3) δ 8.54 (d, J=7.8 Hz, 1H), 8.51 (d, J=7.2 Hz, 1H), 8.24 (d, J=7.4 Hz, 1H), 7.85 (m, 1H), 7.60-7.45 (m, 4H), 6.19 (s, 2H); EIMS m/z (rel intensity) 262 (M+, 100). Anal. (C16H10N2O2.0.25H2O) C, H, N. | Nn1c2c(c3ccccc3c1=O)C(=O)c1ccccc1-2 | null | 75.8 | null |
557,013 | ord_dataset-f483e698250b4da0a84f425c7bfa965a | null | 2002-01-01T00:08:00 | true | [CH2:1]1[CH2:13][O:12][C:11]2[CH:10]=[CH:9][C:5]([CH2:6][CH2:7][NH2:8])=[CH:4][C:3]=2[O:2]1.Cl[C:15]1[C:16]2[C:28]([CH3:29])=[CH:27][S:26][C:17]=2[N:18]=[C:19]([C:21]2[O:25][N:24]=[CH:23][CH:22]=2)[N:20]=1>>[O:25]1[C:21]([C:19]2[N:20]=[C:15]([NH:8][CH2:7][CH2:6][C:5]3[CH:9]=[CH:10][C:11]4[O:12][CH2:13][CH2:1][O:2][C:3]=4[CH:4]=3)[C:16]3[C:28]([CH3:29])=[CH:27][S:26][C:17]=3[N:18]=2)=[CH:22][CH:23]=[N:24]1 | Cc1csc2nc(-c3ccno3)nc(Cl)c12 | NCCc1ccc2c(c1)OCCO2 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | With the procedure of Example 1, the reaction of 3,4-ethylenedioxyphenethylamine with 4-chloro-2-(isoxazol-5-yl)-5-methyl-thieno-[2,3-d]-pyrimidine yields 2-(isoxazol-5-yl)-4-(3,4-ethylenedioxyphenethylamino)-5-methyl-thieno-[2,3-d]-pyrimidine. | Cc1csc2nc(-c3ccno3)nc(NCCc3ccc4c(c3)OCCO4)c12 | null | null | null |
253,669 | ord_dataset-cf82113c6dd341d4a014b4667994f01c | null | 1992-01-01T00:09:00 | true | [O:1]=[C:2]1[N:7]2[N:8]=[CH:9][C:10]3[CH:14]=[CH:13][S:12][C:11]=3[C:6]2=[C:5]([C:15]([OH:17])=[O:16])[CH:4]=[C:3]1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>[OH-].[K+]>[C:9]([C:10]1[CH:14]=[CH:13][S:12][C:11]=1[C:6]1[NH:7][C:2](=[O:1])[C:3]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:4][C:5]=1[C:15]([OH:17])=[O:16])#[N:8] | O=C(O)c1cc(-c2ccccc2)c(=O)n2ncc3ccsc3c12 | null | null | [K+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 48.7 g of 7-oxo-8-phenyl-7H-pyrido[1,2-b]thieno[2,3-d]-pyridazine-10-carboxylic acid were added to a methanolic potassium hydroxide solution (prepared from 72 g of potassium hydroxide and 640 ml of methanol) and the mixture was heated to boiling under reflux for about 24 hours. The reaction mixture was evaporated to half in a vacuum, treated with 80 ml of water and adjusted to pH 1 by the addition of 1N hydrochloric acid. The separated crystals were filtered off under suction, washed with water and dried in a vacuum. There was obtained 48.6 g of 2-(3-cyano-2-thienyl)-1,6-dihydro-6-oxo-5-phenylnicotinic acid as yellow crystals with a m.p. of 255°-257° (methanol/N,N-dimethylformamide). | N#Cc1ccsc1-c1[nH]c(=O)c(-c2ccccc2)cc1C(=O)O | null | 99.8 | null |
616,774 | ord_dataset-31fc6d0085ca4d8dbbcd3a5fa9dcedfb | null | 2003-01-01T00:11:00 | true | [Na+].[C:2]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][S:11](=O)(=[O:13])[O-:12])=[C:6]([O:15][CH3:16])[CH:5]=1)#[N:3].P(Cl)(Cl)(Cl)(Cl)[Cl:18]>O=P(Cl)(Cl)Cl>[C:2]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][S:11]([Cl:18])(=[O:13])=[O:12])=[C:6]([O:15][CH3:16])[CH:5]=1)#[N:3] | ClP(Cl)(Cl)(Cl)Cl | COc1cc(C#N)ccc1NS(=O)(=O)[O-] | null | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O=P(Cl)(Cl)Cl | null | null | null | null | null | null | null | null | null | null | null | null | To a soultion of N-(4-cyano-2-methoxyphenyl)-sulfamic acid sodium salt (1 mmol) at 0° C. in POCl3 (1 mL) is added phosphorous pentachloride (1.2 mmol). Upon reaction completion, the reaction mixture is concentrated and the crude material will be carried onto the next step without further purification. | COc1cc(C#N)ccc1NS(=O)(=O)Cl | null | null | null |
747,077 | ord_dataset-4b705442211b4a3988e26d5f65098160 | null | 2006-01-01T00:12:00 | true | [C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[F:20])=[CH:10][C:9]=1[NH2:21])([CH3:4])([CH3:3])[CH3:2].C([O:25][C:26](=O)[CH2:27][C:28]([C:30]1[CH:35]=[C:34]([C:36]#[N:37])[CH:33]=[CH:32][C:31]=1[F:38])=[O:29])C>>[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[F:20])=[CH:10][C:9]=1[NH:21][C:26](=[O:25])[CH2:27][C:28]([C:30]1[CH:35]=[C:34]([C:36]#[N:37])[CH:33]=[CH:32][C:31]=1[F:38])=[O:29])([CH3:4])([CH3:2])[CH3:3] | CC(C)(C)OC(=O)Nc1ccc(-c2ccccc2F)cc1N | CCOC(=O)CC(=O)c1cc(C#N)ccc1F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Prepared from (3-amino-2′-fluoro-biphenyl-4-yl)-carbamic acid tert.-butyl ester (Example G37) (302 mg, 1.0 mmol) and 3-(5-cyano-2-fluoro-phenyl)-3-oxo-propionic acid ethyl ester (Example H18) (362 mg, 1.5 mmol) according to the general procedure K. Obtained as a yellow-brown solid (352 mg). | CC(C)(C)OC(=O)Nc1ccc(-c2ccccc2F)cc1NC(=O)CC(=O)c1cc(C#N)ccc1F | null | 71.6 | null |
1,454,388 | ord_dataset-a86112d52cd54525a5e36d41f18aced2 | null | 2014-01-01T00:07:00 | true | [C:1]([O:5][C:6]([N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[CH2:17][NH:18][CH:19]1[C:28]2[N:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH2:22][CH2:21][CH2:20]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[O:29]=[C:30]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:32](=[O:39])[N:31]1[CH2:40][CH2:41][C:42]1([CH:45]=O)[CH2:44][CH2:43]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[CH2:17][N:18]([CH2:45][C:42]1([CH2:41][CH2:40][N:31]2[C:30](=[O:29])[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:32]2=[O:39])[CH2:44][CH2:43]1)[CH:19]1[C:28]2[N:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH2:22][CH2:21][CH2:20]1)=[O:7])([CH3:4])([CH3:2])[CH3:3] | CC(C)(C)OC(=O)n1c(CNC2CCCc3cccnc32)nc2ccccc21 | O=CC1(CCN2C(=O)c3ccccc3C2=O)CC1 | null | CC(=O)O[BH-](OC(C)=O)OC(C)=O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | null | null | Using General Procedure B: Reaction of (1-tert-butoxycarbonyl-1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine (0.269 g, 0.70 mmol) and 1-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-cyclopropanecarboxaldehyde (0.25, 1.03 mmol) with NaBH(OAc)3 (0.433 g, 2.04 mmol) in CH2Cl2 (7 mL) for 6 hours followed by purification of the crude material by column chromatography on silica gel (50:1:1 CH2Cl2—CH3OH—NH4OH) followed by radial chromatography on silica gel (1 mm plate, 100:1:1 CH2Cl2—CH3OH—NH4OH) provided 0.125 g (29%) of 2-{[{1-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-cyclopropylmethyl}-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzimidazole-1-carboxylic acid tert-butyl ester as a white foam. | CC(C)(C)OC(=O)n1c(CN(CC2(CCN3C(=O)c4ccccc4C3=O)CC2)C2CCCc3cccnc32)nc2ccccc21 | null | 29.5 | null |
1,036,519 | ord_dataset-3af92aec23dc4810b92eb0d8c60023ee | null | 2011-01-01T00:03:00 | true | [C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[NH:14][N:13]=[C:12]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=3)[C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:25][O:26][C:27]1[CH:34]=[CH:33][C:30]([CH2:31]Cl)=[C:29]([CH3:35])[CH:28]=1.C(C=P(CCCC)(CCCC)CCCC)#N>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[N:14]([CH2:31][C:30]3[CH:33]=[CH:34][C:27]([O:26][CH3:25])=[CH:28][C:29]=3[CH3:35])[N:13]=[C:12]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=3)[C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3] | CC(C)(C)OC(=O)N1CCc2[nH]nc(-c3ccc(Cl)cc3)c2CC1 | COc1ccc(CCl)c(C)c1 | null | CCCCP(=CC#N)(CCCC)CCCC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | 110 | null | To a solution of 3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.4 mmol) in toluene (3 mL) was added 4-methoxy-2-methyl-benzyl chloride (0.9 mmol) and cyanomethylene-tri-n-butylphosphorane (1 mmol). The mixture was heated at 110° C. for 16 h. After concentration and purification (SiO2, EtOAc/hexanes), 3-(4-chloro-phenyl)-1-(4-methoxy-2-methyl-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester was obtained (54 mg). The other regioisomer, 3-(4-chloro-phenyl)-2-(4-methoxy-2-methyl-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester, was also obtained (86 mg). 3-(4-Chloro-phenyl)-1-(4-methoxy-2-methyl-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (20 mg) was treated with TFA (1 mL) in CH2Cl2 (10 mL) for 4 h. After concentration of the reaction mixture, the title compound was obtained (0.02 g). MS (ESI): exact mass calculated for C22H24ClN3O, 381.16. found, m/z 382.1 [M+H]+. 1H NMR (500 MHz, CD3OD): 7.39-7.37 (m, 2H), 7.34-7.32 (m, 2H), 6.68-6.66 (br m, 1H), 6.54-6.52 (br m, 1H), 6.37 (d, J=8.3 Hz, 1H), 5.21 (s, 2H), 2.81-2.79 (m, 4H), 2.71-2.69 (m, 4H). | COc1ccc(Cn2nc(-c3ccc(Cl)cc3)c3c2CCN(C(=O)OC(C)(C)C)CC3)c(C)c1 | null | null | null |
1,623,772 | ord_dataset-35c51552812941cda45194a013d34bb9 | null | 2015-01-01T00:08:00 | true | C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]([O:23][CH2:24][C:25]([NH:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]#[N:35])=[C:30]([O:36][C:37]([F:40])([F:39])[F:38])[CH:29]=1)=O)(=[O:22])[CH3:21].C[Si]([N:45]=[N+:46]=[N-:47])(C)C>C1COCC1>[C:20]([O:23][CH2:24][C:25]1[N:27]([C:28]2[CH:33]=[CH:32][C:31]([C:34]#[N:35])=[C:30]([O:36][C:37]([F:40])([F:39])[F:38])[CH:29]=2)[N:47]=[N:46][N:45]=1)(=[O:22])[CH3:21] | C[Si](C)(C)N=[N+]=[N-] | CC(=O)OCC(=O)Nc1ccc(C#N)c(OC(F)(F)F)c1 | null | c1ccc(P(c2ccccc2)c2ccccc2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | 0.5 | Triphenylphosphine (17.29 g, 65.7 mmol) and diisopropylazodicorboxylate (13.3 g, 65.7 mmol) were added to a solution of 2-({4-cyano-3-[(trifluoromethyl)oxy]phenyl}amino)-2-oxoethyl acetate (Intermediate 52, 8.0 g, 26.5 mmol) in THF (160 mL) at 0° C. and the mixture was stirred for 30 min. Trimethylsilyl azide (7.60 g, 66.0 mmol) was added dropwise at room temperature and the mixture was heated to reflux for 4 hr. THF was removed under reduced pressure and the residue was diluted with EtOAc and washed with ice-cooled water. The extracted organic layer was washed with brine solution, dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford the crude product. This was purified by column chromatography (100-200 mesh silica gel), eluting with 20% EtOAc/pet ether to give the title compound (7.0 g). | CC(=O)OCc1nnnn1-c1ccc(C#N)c(OC(F)(F)F)c1 | null | 80.7 | null |
174,640 | ord_dataset-4937da99a6a247eb90fa70f0d2eac3db | null | 1988-01-01T00:07:00 | true | [CH3:1][C:2]1[NH:3][C:4]([CH3:46])=[C:5]([C:21]([O:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][N:35]2C(=O)C3=CC=CC=C3C2=O)=[O:22])[CH:6]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[C:7]=1[C:8]([O:10][CH3:11])=[O:9].O.NN>>[CH3:1][C:2]1[NH:3][C:4]([CH3:46])=[C:5]([C:21]([O:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][NH2:35])=[O:22])[CH:6]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[C:7]=1[C:8]([O:10][CH3:11])=[O:9] | COC(=O)C1=C(C)NC(C)=C(C(=O)OCCCCCCCCCCCN2C(=O)c3ccccc3C2=O)C1c1cccc([N+](=O)[O-])c1 | null | null | NN | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | null | null | null | null | null | null | null | null | null | null | null | null | Prepared by a method analogous to that of Example 1(b) from 18.95 g (30 mmol) of 1,4-dihydro-2,6-dimethyl-3-methoxycarbonyl-4-(3-nitrophenyl)-5-(11-phthalimido-undecyloxy)carbonyl-pyridine and 4.5 ml (90 mmol) of hydrazine hydrate. 15.0 g of a yellow oil which is used for further reactions without purification. | COC(=O)C1=C(C)NC(C)=C(C(=O)OCCCCCCCCCCCN)C1c1cccc([N+](=O)[O-])c1 | null | null | null |
1,014,957 | ord_dataset-f024e9664ab64906a71a2ff6004cb3d0 | null | 2010-01-01T00:12:00 | true | C(O[C:6]([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][OH:15])[CH2:9]1)=O)(C)(C)C.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH3:6][N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][OH:15])[CH2:9]1 | CC(C)(C)OC(=O)N1CCO[C@H](CO)C1 | null | null | [Al+3] | [H-] | [Li+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | 0.25 | (S)-2-Hydroxymethyl-morpholine-4-carboxylic acid tert-butyl ester (Intermediate 8; 1.20 g, 5.52 mmol) in THF (5 mL) was added to a suspension of LiAlH4 (1.30 g, 34.3 mmol) in anhydrous THF (15 mL) at −10° C. and stirred under nitrogen for 15 min. The cooling bath was removed and the reaction mixture was gently heated to reflux for 4 h. The reaction mixture was quenched by careful addition of a mixture of water (4 mL) in THF (25 mL) with ice bath cooling. THF (50 mL) was added to the reaction mixture, stirred for 15 min, filtered and the solid washed with THF (50 mL). The combined filtrates were evaporated in vacuo. The residue was dissolved in DCM (50 mL), dried (MgSO4) and the solvent removed in vacuo to give (S)-(4-methylmorpholin-2-yl)-methanol (490 mg, 67%) as a colourless oil. | CN1CCO[C@H](CO)C1 | null | 67.7 | null |
931,609 | ord_dataset-d8a5dc784dde4465894ec7c69d2e3ba6 | null | 2010-01-01T00:01:00 | true | [CH:1]1([N:6]2[C:11]3[N:12]=[C:13]([S:16][CH3:17])[N:14]=[CH:15][C:10]=3[CH:9]=[C:8]([C:18]3[CH:23]=[C:22]([C:24]4[O:25][C:26]([CH2:29][CH:30]([CH3:32])[CH3:31])=[N:27][N:28]=4)[CH:21]=[CH:20][C:19]=3[CH3:33])[C:7]2=[O:34])[CH2:5][CH2:4][CH2:3][CH2:2]1.ClC1C=C(C=CC=1)C(OO)=[O:40]>ClCCl.C(OCC)(=O)C>[CH:1]1([N:6]2[C:11]3[N:12]=[C:13]([S:16]([CH3:17])=[O:40])[N:14]=[CH:15][C:10]=3[CH:9]=[C:8]([C:18]3[CH:23]=[C:22]([C:24]4[O:25][C:26]([CH2:29][CH:30]([CH3:32])[CH3:31])=[N:27][N:28]=4)[CH:21]=[CH:20][C:19]=3[CH3:33])[C:7]2=[O:34])[CH2:2][CH2:3][CH2:4][CH2:5]1 | CSc1ncc2cc(-c3cc(-c4nnc(CC(C)C)o4)ccc3C)c(=O)n(C3CCCC3)c2n1 | O=C(OO)c1cccc(Cl)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOC(C)=O | ClCCl | null | null | null | null | null | null | null | null | null | 0 | 1 | To a solution of 8-cyclopentyl-6-{5-(5-isobutyl-[1,3,4]oxadiazol-2-yl)-2-methyl-phenyl}-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one (40.0 mg, 0.08 mmol) in dichloromethane (3 mL) at 0° C. was added 3-chloroperoxybenzoic acid (0.04 g, 0.19 mmol). The mixture was stirred at 0° C. for 1 hour, then was diluted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution and brine, dried (magnesium sulfate), filtered and concentrated under reduced pressure to give 8-cyclopentyl-6-{5-(5-isobutyl-[1,3,4]-oxadiazol-2-yl)-2-methyl-phenyl}-2-methanesulfinyl-8H-pyrido[2,3-d]pyrimidin-7-one (0.06 g). The crude product was used in the next step without further purification. | Cc1ccc(-c2nnc(CC(C)C)o2)cc1-c1cc2cnc(S(C)=O)nc2n(C2CCCC2)c1=O | null | 152.6 | null |
955,788 | ord_dataset-ed65749688da45af8a8432967b017729 | null | 2010-01-01T00:05:00 | true | ClCC([NH:5][C:6]1[C:11]([N+:12]([O-:14])=[O:13])=[CH:10][CH:9]=[C:8]([F:15])[C:7]=1[CH3:16])=O.[OH-].[Na+].O1CCCC1>O>[F:15][C:8]1[C:7]([CH3:16])=[C:6]([C:11]([N+:12]([O-:14])=[O:13])=[CH:10][CH:9]=1)[NH2:5] | Cc1c(F)ccc([N+](=O)[O-])c1NC(=O)CCl | null | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | 2-Chloro-N-(3-fluoro-2-methyl-6-nitrophenyl)acetamide (prepared from 47.2 g of 2-chloro-N-(3-fluoro-2-methylphenyl)acetamide, ca. 234 mmol) was suspended in water (220 ml) then treated with aqueous sodium hydroxide solution (12.5M, 110 ml, 1.37 mol). Tetrahydrofuran (110 ml) was added, then the mixture was heated to reflux for 5 hours, then evaporated (removing most of the tetrahydrofuran). The yellow solid was filtered off and washed with water until washing were non-alkaline. Drying in vacuo afforded a yellow solid (32.3 g, 81% over 2 steps) containing ˜13% isomer. | Cc1c(F)ccc([N+](=O)[O-])c1N | null | null | null |
1,078,050 | ord_dataset-afd812677c134591a99f46ce28de2524 | null | 2011-01-01T00:08:00 | true | Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[C:19]2[C:20]([F:34])=[C:21]([NH:25][S:26]([C:29]3[CH:33]=[CH:32][O:31][CH:30]=3)(=[O:28])=[O:27])[CH:22]=[CH:23][CH:24]=2)[CH:5]=[CH:4][N:3]=1.[CH3:35][Zn]C>>[F:34][C:20]1[C:19]([C:9]2[N:10]=[C:11]([CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[S:12][C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([CH3:35])[N:7]=2)=[CH:24][CH:23]=[CH:22][C:21]=1[NH:25][S:26]([C:29]1[CH:33]=[CH:32][O:31][CH:30]=1)(=[O:28])=[O:27] | C[Zn]C | O=S(=O)(Nc1cccc(-c2nc(C3CCOCC3)sc2-c2ccnc(Cl)n2)c1F)c1ccoc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Following a procedure analogous to the procedure described in Example 25 using N-{3-[5-(2-chloro-4-pyrimidinyl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazol-4-yl]-2-fluorophenyl}-3-furansulfonamide (200 mg, 0.384 mmol)mmol) and dimethylzinc (384 μl, 0.768 mmol) at 80° C. for 3 hours, the title compound was obtained as a solid (60 mg, 31% yield). MS (ESI): 500.8 [M+H]+ | Cc1nccc(-c2sc(C3CCOCC3)nc2-c2cccc(NS(=O)(=O)c3ccoc3)c2F)n1 | null | null | null |
1,417,781 | ord_dataset-f8e6e6a2d2bf4135b9e346456c81700f | null | 2014-01-01T00:04:00 | true | Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1.Cl.[F:12][C:13]1([F:19])[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.C(N(CC)C(C)C)(C)C>C(O)C>[F:12][C:13]1([F:19])[CH2:18][CH2:17][N:16]([C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=2)[CH2:15][CH2:14]1 | FC1(F)CCNCC1 | O=[N+]([O-])c1ccc(Cl)nc1 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | CCN(C(C)C)C(C)C | null | null | null | null | null | null | null | null | null | 70 | null | To a slurry of 2-chloro-5-nitropyridine (5 g, 31.5 mmol) and 4,4-difluoropiperidine hydrochloride (4.97 g) in ethanol (40 mL) at ambient temperature was added N,N-diisopropylethylamine (12.00 mL, 69.4 mmol) and the mixture heated to 70° C. for 18 hours. The reaction was concentrated, partitioned between CH2Cl2 and 1M NaOH. The organic phase concentrated and purified by chromatography (elution with 2% MeOH—CH2Cl2 then 3% MeOH—CH2Cl2) to provide the title compound as a yellow oil. MS (DCI) m/z 261 (M+NH4)+. | O=[N+]([O-])c1ccc(N2CCC(F)(F)CC2)nc1 | null | null | null |
653,058 | ord_dataset-fe016e2f90e741a590ad77fd5933161f | null | 2004-01-01T00:11:00 | true | C([O:8][C:9]1[CH:25]=[CH:24][C:12]([CH2:13][NH:14][C:15]2[C:20]([Cl:21])=[C:19](C)[N:18]=[C:17]([CH3:23])[N:16]=2)=[CH:11][C:10]=1[O:26][CH:27]([F:29])[F:28])C1C=CC=CC=1.Cl.[CH2:31](O)C>>[Cl:21][C:20]1([CH3:31])[CH:19]=[N:18][C:17]([CH3:23])=[N:16][CH:15]1[NH:14][CH2:13][C:12]1[CH:24]=[CH:25][C:9]([OH:8])=[C:10]([O:26][CH:27]([F:28])[F:29])[CH:11]=1 | CCO | Cc1nc(C)c(Cl)c(NCc2ccc(OCc3ccccc3)c(OC(F)F)c2)n1 | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | In analogy to the method described in example B1, 6.9 g (16.4 mmol) of [4-benzyloxy-3-(1.1-difluoromethoxy)benzyl](5-chloro-2,6-dimethylpyrimidin-4-yl)amine (from example A6) are reacted with 70 ml of 12.5N hydrochloric acid in 70 ml of ethanol. Extraction with ethyl acetate at a pH of 8 gives, after concentration, a solid residue. Extraction by stirring with petroleum ether and drying give 2.2 g (41%) of the title compound as a beige crystallizate. m.p.: 167-168.5° C. | CC1=NC(NCc2ccc(O)c(OC(F)F)c2)C(C)(Cl)C=N1 | null | 41 | null |
1,051,059 | ord_dataset-dd320ded4b3f4764af39de99491533f7 | null | 2011-01-01T00:04:00 | true | [C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6](Cl)=[O:7])#[CH:2].[C:12]1([OH:18])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.N1C=CC=CC=1>ClCCl>[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6]([O:18][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:7])#[CH:2] | Oc1ccccc1 | C#Cc1cccc(C(=O)Cl)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | c1ccncc1 | null | null | null | null | null | null | null | null | null | null | null | Air in a 20 ml Schlenk tube was replaced by Ar gas and 1.02 g (7 mmol) of m-ethynylbenzoic acid and 5 g (42 mmol) of thionyl chloride were added to the tube and the mixture was stirred at 50° C. for 2 hours and then excess thionyl chloride was removed by distillation under reduced pressure to obtain m-ethynylbenzoyl chloride. To the m-ethynylbenzoyl chloride obtained was added a solution having 692 mg (7.35 mmol) of phenol and 3.4 ml (42 mmol) of pyridine dissolved in 7 ml of dichloromethane under ice-cooling and then the resultant mixture was stirred at room temperature for one hour. After completion of the stirring, dichloromethane was removed by distillation under reduced pressure and 35 ml of water was added to the resultant residue. The mixture was extracted with 35 ml of ethyl acetate, the extract was dried over magnesium sulfate and the solvent was removed by distillation under reduced pressure using an evaporator. The resultant crude reaction product was purified by column chromatography (Hexane/AcOEt=10/1) using silica gel to obtain 0.55 q of phenyl 3-ethynylbenzoate which is a desired product as yellow solid. (Yield: 35%) | C#Cc1cccc(C(=O)Oc2ccccc2)c1 | null | null | null |
153,173 | ord_dataset-128a4f3f44e844218b1c319ab4de3893 | null | 1987-01-01T00:02:00 | true | Cl[Si:2]([CH3:10])([CH3:9])[CH2:3][CH2:4][Si:5](Cl)([CH3:7])[CH3:6].[NH2:11][CH:12]1[C:33](=[O:34])[N:14]2[C:15]([C:20]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][CH:25]=3)=[O:21])=[C:16]([Cl:19])[CH2:17][S:18][C@H:13]12.C(N(CC)CC)C>C(Cl)Cl>[Cl:19][C:16]1[CH2:17][S:18][C@@H:13]2[CH:12]([N:11]3[Si:5]([CH3:7])([CH3:6])[CH2:4][CH2:3][Si:2]3([CH3:10])[CH3:9])[C:33](=[O:34])[N:14]2[C:15]=1[C:20]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][CH:25]=1)=[O:21] | NC1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(Cl)CS[C@H]12 | C[Si](C)(Cl)CC[Si](C)(C)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CCN(CC)CC | null | null | null | null | null | null | null | null | null | 25 | null | A solution of 1,2-bis(chlorodimethylsilyl)ethane (3.2 g) in methylene chloride (20 ml) was added to a stirred mixture of p-nitrobenzyl 7-amino-3-chloro-3-cephem-4-carboxylate (5.0 g) and triethylamine (4.9 ml) in methylene chloride (25 ml) under a nitrogen atmosphere. The mixture was stirred at reflux for 16 hours, then allowed to cool to room temperature, and washed with 8% aqueous sodium hydrogen phosphate solution. The organic layer was separated, dried with magnesium sulphate, and evaporated under reduced pressure to give the title compound as a gum, nmr (CDCl3) δ0.17 (s, 12H), 0.78 (s, 4H), 3.38+3.82 (ABq, J=18 Hz, 2H), 4.76 (d, J=4 Hz, 1H), 4.93 (d, J=4 Hz, 1H), 5.28 (s, 2H), 7.3-8.1 (m, 4H). | C[Si]1(C)CC[Si](C)(C)N1C1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(Cl)CS[C@H]12 | null | null | null |
821,743 | ord_dataset-ec58fad8331a42c5a67ad75aac6713b4 | null | 2008-01-01T00:05:00 | true | [NH2:1][CH:2]1[C:8](=[O:9])[N:7]([CH3:10])[C:6]2[CH:11]=[CH:12][CH:13]=[CH:14][C:5]=2[C:4]2[CH:15]=[CH:16][CH:17]=[CH:18][C:3]1=2.[CH3:19][CH:20]([C:24]([NH:26][CH2:27][C:28]1[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=1)=[O:25])[C:21](O)=[O:22]>>[CH3:19][CH:20]([C:21]([NH:1][CH:2]1[C:8](=[O:9])[N:7]([CH3:10])[C:6]2[CH:11]=[CH:12][CH:13]=[CH:14][C:5]=2[C:4]2[CH:15]=[CH:16][CH:17]=[CH:18][C:3]1=2)=[O:22])[C:24]([NH:26][CH2:27][C:28]1[CH:29]=[CH:30][C:31]([CH3:34])=[CH:32][CH:33]=1)=[O:25] | Cc1ccc(CNC(=O)C(C)C(=O)O)cc1 | CN1C(=O)C(N)c2ccccc2-c2ccccc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound, MS: m/e=441.2 (M+H+), was prepared in analogy to example 16 from 7-amino-5-methyl-5H,7H-dibenzo[b,d]azepin-6-one and 2-methyl-N-(4-methyl-benzyl)-malonamic acid. | Cc1ccc(CNC(=O)C(C)C(=O)NC2C(=O)N(C)c3ccccc3-c3ccccc32)cc1 | null | null | null |
1,747,553 | ord_dataset-60a3e71da3174666a50a61dcfa611a9f | null | 2016-01-01T00:07:00 | true | [OH:1][NH:2][C:3]1[CH:13]=[CH:12][CH:11]=[CH:10][C:4]=1[C:5]([O:7][CH2:8][CH3:9])=[O:6].Br[CH2:15][C:16]1[N:17]=[C:18]([C:21]([F:24])([F:23])[F:22])[S:19][CH:20]=1>>[F:22][C:21]([F:24])([F:23])[C:18]1[S:19][CH:20]=[C:16]([CH2:15][O:1][NH:2][C:3]2[CH:13]=[CH:12][CH:11]=[CH:10][C:4]=2[C:5]([O:7][CH2:8][CH3:9])=[O:6])[N:17]=1 | FC(F)(F)c1nc(CBr)cs1 | CCOC(=O)c1ccccc1NO | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The titled compound was prepared using similar procedure as that of Example-1 (step-2) using ethyl 2-(hydroxyamino)benzoate and product of step 3 described above in 52% yield. | CCOC(=O)c1ccccc1NOCc1csc(C(F)(F)F)n1 | null | 52 | null |
1,548,302 | ord_dataset-cac8df8aff894288876df4e093c9877f | null | 2015-01-01T00:02:00 | true | [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([OH:12])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH:38]1[CH2:41][CH:40]([C:42]2[C:47]([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)=[CH:46][CH:45]=[CH:44][N:43]=2)[CH2:39]1>CN(C=O)C.O>[NH:3]1[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[N:1]=[C:2]1[C:10]([N:38]1[CH2:39][CH:40]([C:42]2[C:47]([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)=[CH:46][CH:45]=[CH:44][N:43]=2)[CH2:41]1)=[O:12] | c1ccc(-c2cccnc2C2CNC2)cc1 | O=C(O)c1nc2ccccc2[nH]1 | null | CN(C)C(On1nnc2cccnc21)=[N+](C)C | Cl | F[P-](F)(F)(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 0.08 | To a mixture of 1H-benzoimidazole-2-carboxylic acid (124 mg, 0.76 mmol) in DMF (5 mL) was added TEA (152 mg, 1.5 mmol) and HATU (347 mg, 0.92 mmol). The reaction mixture was stirred for 5 min and 2-azetidin-3-yl-3-phenyl-pyridine hydrochloride (100 mg, 0.76 mmol) was added. The reaction mixture was stirred at RT overnight. The mixture was diluted with water (10 mL), and extracted with EtOAc (2×20 mL). The combined organic extracts were washed with water (5 mL) and brine (5 mL), dried over Na2SO4, and filtered. The filtrate was evaporated in vacuo and the residue was purified by column chromatography to give (1H-benzoimidazol-2-yl)-[3-(3-phenyl-pyridin-2-yl)-azetidin-1-yl]-methanone (100 mg, 0.28 mmol, 59% yield) as a light yellow solid. | O=C(c1nc2ccccc2[nH]1)N1CC(c2ncccc2-c2ccccc2)C1 | null | 36.8 | null |
1,429,570 | ord_dataset-5e6956e6e8c24a168866a253f4a66c6c | null | 2014-01-01T00:05:00 | true | [C:1]([C:3]1[CH:27]=[CH:26][C:6]([O:7][C:8]2[CH:9]=[C:10]([CH:14]=[C:15]([O:17][C:18]3[CH:23]=[CH:22][C:21]([C:24]#[N:25])=[CH:20][CH:19]=3)[CH:16]=2)[C:11](O)=[O:12])=[CH:5][CH:4]=1)#[N:2].[C:28]([O:32][C:33]([N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1)=[O:34])(C)(C)[CH3:29]>>[CH2:28]([O:32][C:33]([N:35]1[CH2:36][CH2:37][N:38]([C:11](=[O:12])[C:10]2[CH:14]=[C:15]([O:17][C:18]3[CH:19]=[CH:20][C:21]([C:24]#[N:25])=[CH:22][CH:23]=3)[CH:16]=[C:8]([O:7][C:6]3[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:27][CH:26]=3)[CH:9]=2)[CH2:39][CH2:40]1)=[O:34])[CH3:29] | N#Cc1ccc(Oc2cc(Oc3ccc(C#N)cc3)cc(C(=O)O)c2)cc1 | CC(C)(C)OC(=O)N1CCNCC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Following the procedure of Example 5(c) 3,5-bis-(4-cyano-phenoxy)-benzoic acid 0.45 g (1.26 mmol) and piperazine-1-carboxylic acid tert-butyl ester (0.234 g, 1.26 mmol) were used to afford 0.5 g of the required product. 1H NMR (DMSO-d6): δ 1.18 (3H, t), 3.52 (8H, m), 4.15 (2H, q), 7.00 (2H, s), 7.07 (1H, s), 7.28 (2H, d), 7.88 (2H, d). | CCOC(=O)N1CCN(C(=O)c2cc(Oc3ccc(C#N)cc3)cc(Oc3ccc(C#N)cc3)c2)CC1 | null | 79.9 | null |
1,152,194 | ord_dataset-b195433d5c354ddfb6cde0d53c41910f | null | 2012-01-01T00:04:00 | true | Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([Cl:12])=[N:4][N:3]=1.[CH3:13][C@H:14]1[CH2:19][NH:18][C@H:17]([CH3:20])[CH2:16][NH:15]1>ClCCl>[Cl:12][C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]([N:15]2[CH2:16][C@@H:17]([CH3:20])[NH:18][CH2:19][C@@H:14]2[CH3:13])=[N:3][N:4]=1 | C[C@@H]1CN[C@@H](C)CN1 | Clc1nnc(Cl)c2ccccc12 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 130 | null | 1,4-dichlorophthalazine (1.0 g, 5 mmole) and trans-2,5-dimethyl piperazine were combined in a reaction vial and heated to 130° C. for 3 h with stirring. After cooling to room temperature, the solid residue was dissolved in 150 mL of dichloromethane and washed with 1×20 mL of 1:1 saturated NaHCO3 solution:H2O and 1×20 mL of saturated NaCl solution. The organic phase was dried over MgSO4, filtered, and concentrated. Purification by column chromatography (100:5:1 dichloromethane:methanol:triethylamine) afforded 1-chloro-4-(trans-2,5-dimethylpiperazin-1-yl)phthalazine. MS (M+H)+=277.1. | C[C@@H]1CN(c2nnc(Cl)c3ccccc23)[C@@H](C)CN1 | null | null | null |
626,895 | ord_dataset-e44331dc51de453ca14b7032593c1958 | null | 2004-01-01T00:02:00 | true | [NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[O:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[N:5]=[CH:4][N:3]=1.[CH3:21][O:22][C:23]1[CH:24]=[C:25]([N:29]=[C:30]=[O:31])[CH:26]=[CH:27][CH:28]=1>ClCCl>[CH3:20][O:19][C:16]1[CH:17]=[CH:18][C:13]([O:12][C:10]2[CH:9]=[CH:8][CH:7]=[C:6]3[C:11]=2[C:2]([NH:1][C:30]([NH:29][C:25]2[CH:26]=[CH:27][CH:28]=[C:23]([O:22][CH3:21])[CH:24]=2)=[O:31])=[N:3][CH:4]=[N:5]3)=[CH:14][CH:15]=1 | COc1ccc(Oc2cccc3ncnc(N)c23)cc1 | COc1cccc(N=C=O)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | null | null | 4-Amino-5-(4-methoxyphenoxy)quinazoline (0.35 g, 1.3 mmol) and 3-methoxyphenyl isocyanate (0.23 g, 1.6 mmol) were reacted in 20 ml of dichloromethane according to procedure E to give 1-[5-(4-methoxyphenoxy)quinazolin-4-yl]-3-(3-methoxyphenyl)urea (0.4 g, 74.1%, m.p. 209-210° C.). | COc1ccc(Oc2cccc3ncnc(NC(=O)Nc4cccc(OC)c4)c23)cc1 | null | 73.9 | null |
351,542 | ord_dataset-127eb5fdd5b4402e92b51d0b55a5dcb5 | null | 1997-01-01T00:01:00 | true | [CH3:1][O:2][CH2:3][C:4]([Cl:6])=[O:5].[Cl-].[C:8]([O:11][CH:12]([CH2:30][O:31][C:32](=[O:34])[CH3:33])[CH2:13][NH:14][C:15](=[O:29])[C:16]1[C:24]([I:25])=[C:23]([NH2:26])[C:22]([I:27])=[C:18]([C:19]([OH:21])=[O:20])[C:17]=1[I:28])(=[O:10])[CH3:9]>O1CCOCC1>[Cl-:6].[C:8]([O:11][CH:12]([CH2:30][O:31][C:32](=[O:34])[CH3:33])[CH2:13][NH:14][C:15](=[O:29])[C:16]1[C:24]([I:25])=[C:23]([NH:26][C:4](=[O:5])[CH2:3][O:2][CH3:1])[C:22]([I:27])=[C:18]([C:19]([OH:21])=[O:20])[C:17]=1[I:28])(=[O:10])[CH3:9] | COCC(=O)Cl | CC(=O)OCC(CNC(=O)c1c(I)c(N)c(I)c(C(=O)O)c1I)OC(C)=O | null | [Cl-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1COCCO1 | null | null | null | null | null | null | null | null | null | null | 25 | null | 24.7 g (150 mmol) of methoxyacetyl chloride is added to a suspension of 73.4 g (100 mmol) of 5-amino-2,4,6-triiodoisophthalic acid-N-(2,3-diacetoxypropyl)-amide-chloride (EP 0308364) in 500 ml of anhydrous dioxane, stirred with exclusion of moisture, at room temperature. The batch is refluxed for several hours, until, according to thin-layer chromatography, feedstock is no longer detectable, then it is concentrated by evaporation, the residue is taken up in dichloromethane and shaken out with saturated aqueous sodium bicarbonate solution. After drying on anhydrous magnesium sulfate, the organic phase is concentrated by evaporation, and the residue is recrystallized from ethyl acetate/tert-butyl methyl ether. | COCC(=O)Nc1c(I)c(C(=O)O)c(I)c(C(=O)NCC(COC(C)=O)OC(C)=O)c1I | null | null | null |
818,778 | ord_dataset-50f99930fc41474db226bc80774b38df | null | 2008-01-01T00:04:00 | true | [CH2:1]([N:8]1[C:13]2[S:14][CH:15]=[C:16]([CH3:17])[C:12]=2[C:11](=[O:18])O[C:9]1=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:20]([O:22][C:23]([C:25]1C(=O)N(CC2C=CC=CC=2)C2SC=CC=2C=1O)=[O:24])[CH3:21]>>[CH2:20]([O:22][C:23]([C:25]1[C:9](=[O:19])[N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:13]2[S:14][CH:15]=[C:16]([CH3:17])[C:12]=2[C:11]=1[OH:18])=[O:24])[CH3:21] | CCOC(=O)c1c(O)c2ccsc2n(Cc2ccccc2)c1=O | Cc1csc2c1c(=O)oc(=O)n2Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | This compound was prepared from 1-benzyl-5-methyl-1H-thieno[2,3-d][1,3]oxazine-2,4-dione (59) by applying the same method described for the preparation of 7-benzyl-4-hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b]pyridine-5-carboxylic acid ethyl ester (60). Yield 80%; MP 166° C. 1H-NMR (DMSO-d6): δ 1.32 (t, J=6.8 Hz, 3H), 2.40 (d, J=1.2 Hz, 3H), 4.36 (q, J=6.8 Hz, 2H), 5.22 (s, 2H), 6.84 (d, J=1.2 Hz, 1H), 7.25 (m, 3H), 7.32 (m, 2H), 14.04 (b, 1H) ppm; EIMS m/z 344 (M+1). | CCOC(=O)c1c(O)c2c(C)csc2n(Cc2ccccc2)c1=O | null | 80 | null |
180,726 | ord_dataset-ed5a3d1f8dc744759e7fa1c320a44e59 | null | 1988-01-01T00:11:00 | true | [CH3:1][C:2]1([C:7]2[CH:8]=[CH:9][C:10]3[CH:14]=[C:13]([S:15](=[O:18])(=[O:17])[NH2:16])[S:12][C:11]=3[CH:19]=2)OCC[O:3]1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(C)=O>[C:2]([C:7]1[CH:8]=[CH:9][C:10]2[CH:14]=[C:13]([S:15](=[O:18])(=[O:17])[NH2:16])[S:12][C:11]=2[CH:19]=1)(=[O:3])[CH3:1] | CC1(c2ccc3cc(S(N)(=O)=O)sc3c2)OCCO1 | null | null | Cc1ccc(S(=O)(=O)O)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(C)=O | null | null | null | null | null | null | null | null | null | null | null | 8 | The ketal product from Example 37 (4.4 g, 14.7 mmole) and p-toluenesulfonic acid (400 mg) were dissolved in acetone (90 ml). The mixture was stirred overnight. The solvent was removed in vacuo and the residue partitioned between ethyl acetate (200 ml) and 10% saturated NaHCO3 solution (b 100 ml). The organic layer was washed with H2O (2×100 ml) and dried over Na2SO4. The solvent was removed in vacuo and the residue was triturated with hot CHCl3 (100 ml). Upon cooling, 3.4 g (90.6%) of product was obtained, m.p. 154°-155° C. | CC(=O)c1ccc2cc(S(N)(=O)=O)sc2c1 | null | 90.6 | null |
374,601 | ord_dataset-ee5599340390470d8e5b5ac1feddf9d6 | null | 1997-01-01T00:08:00 | true | [C:1]([NH:4][C:5]1[CH:14]=[C:13]([F:15])[C:12]([F:16])=[C:11]2[C:6]=1[CH2:7][CH2:8][CH2:9][C:10]2=O)(=[O:3])[CH3:2].C(O)C.[BH4-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)(Cl)Cl>[C:1]([NH:4][C:5]1[CH:14]=[C:13]([F:15])[C:12]([F:16])=[C:11]2[C:6]=1[CH2:7][CH2:8][CH2:9][CH2:10]2)(=[O:3])[CH3:2] | CC(=O)Nc1cc(F)c(F)c2c1CCCC2=O | null | null | O=C(O)CC(O)(CC(=O)O)C(=O)O | [BH4-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClC(Cl)Cl | CCO | null | null | null | null | null | null | null | null | null | 25 | null | The compound obtained in (5) above (1 gm) was dissolved into 20 ml of ethanol. To the solution was added 166 mg of sodium borohydride while stirring at room temperature. After stirring for 20 minutes, chloroform and 10% citric acid were added to the reaction mixture. The chloroform layer was extracted and concentrated. To the concentrate were added 20 ml of toluene and a small amount of p-TsOH, followed by heating under reflux for 1 hour. Upon addition of 100 ml of ethyl acetate, the reaction product was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated and the residue was dissolved into a mixed solvent of 20 ml of ethanol, 20 ml of dioxane, and 0.2 ml of acetic acid. The mixture was catalytically hydrogenated with the addition of 200 mg of platinum oxide. The catalyst was removed, the filtrate was concentrated, and ether was added to the concentrate. 0.8 gm of the title compound was obtained by collecting the precipitate by filtration. | CC(=O)Nc1cc(F)c(F)c2c1CCCC2 | null | null | null |
981,511 | ord_dataset-35b56288528641309a040cc2b6710b61 | null | 2010-01-01T00:08:00 | true | [CH3:1][C:2]([CH3:16])([CH3:15])[C:3](=[O:14])[CH2:4][N:5]1[CH2:12][CH:11]2[O:13][CH:7]([CH2:8][NH:9][CH2:10]2)[CH2:6]1.CS(O[CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[CH:26][CH:25]=1)(=O)=O>CC#N>[CH3:1][C:2]([CH3:16])([CH3:15])[C:3](=[O:14])[CH2:4][N:5]1[CH2:12][CH:11]2[O:13][CH:7]([CH2:8][N:9]([CH2:22][CH2:23][C:24]3[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[CH:26][CH:25]=3)[CH2:10]2)[CH2:6]1 | CS(=O)(=O)OCCc1ccc(C#N)cc1 | CC(C)(C)C(=O)CN1CC2CNCC(C1)O2 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC#N | null | null | null | null | null | null | null | null | null | null | 50 | 24 | A mixture of 3,3-dimethyl-1-(9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl)-2-butanone (from step (ii) above; 56 mg, 0.25 mmol), TEA (0.35 mL, 2.5 mmol) and MeCN (2 mL) was treated with 4-cyanophenethyl methanesulfonate (see step (iii) above; 84 mg, 0.37 mmol). The resulting mixture was stirred at 50° C. for 24 h. The solvents were removed by evaporation, the crude product was dissolved in DCM and then the solution was added to an ion-exchange solid-phase extraction plug (2 g, CBA (carboxylic acid on silica support)). After 1 h, the plug was washed with DCM (15 mL), after which the product was finally eluted with DCM:MeOH:TEA (90:5:5), to give 84 mg (95%) of the title compound. | CC(C)(C)C(=O)CN1CC2CN(CCc3ccc(C#N)cc3)CC(C1)O2 | null | 95 | null |
411,124 | ord_dataset-fbdd058349aa456f812e3546c84baab5 | null | 1998-01-01T00:09:00 | true | Cl.[NH2:2][CH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C:4]1=[O:21].C(=O)([O-])[O-].[K+].[K+].[C:28](#[N:31])[CH:29]=[CH2:30]>CS(C)=O>[NH2:2][C:3]1([CH2:30][CH2:29][C:28]#[N:31])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C:4]1=[O:21] | C=CC#N | COc1ccc2c(c1)C(N)C(=O)N2c1ccc(F)cc1 | null | Cl | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CS(C)=O | null | null | null | null | null | null | null | null | null | null | 25 | 2 | A mixture of 60 g of 3-amino-1-(4-fluorophenyl)-2,3-dihydro-5-methoxy-1H-indol-2-one hydrochloride, 43 g of potassium carbonate, 20 ml of acrylonitrile and 200 ml of dimethyl sulfoxide was stirred at room temperature under argon atmosphere for 2 hours. 2 ml of acrylonitrile was added to the mixture, and stirring was continued overnight. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with a saturated sodium chloride solution, dried over anhydrous magnesium sulfate and filtered, the filtrate was concentrated under reduced pressure. Precipitated crystals were collected by filtration to afford 46.8 g of 3-[3-amino-1-(4-fluorophenyl)-2,3-dihydro-5-methoxy-2-oxo-1H-indol-3-yl]propanenitrile. Melting point 136° to 138° C. EI-MS (m/z): 325 (M+). | COc1ccc2c(c1)C(N)(CCC#N)C(=O)N2c1ccc(F)cc1 | null | null | null |
822,895 | ord_dataset-ec58fad8331a42c5a67ad75aac6713b4 | null | 2008-01-01T00:05:00 | true | [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:14]2[CH:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[N:17]3[N:24]=[CH:25][C:26]([C:27]([OH:29])=O)=[C:16]3[N:15]=2)[CH:7]=[CH:8][C:9]=1[C:10]([F:13])([F:12])[F:11])[CH3:2].[NH2:30][C:31]1[CH:32]=[C:33]([S:37]([NH:40][CH2:41][CH3:42])(=[O:39])=[O:38])[CH:34]=[CH:35][CH:36]=1>>[CH2:41]([NH:40][S:37]([C:33]1[CH:32]=[C:31]([NH:30][C:27]([C:26]2[CH:25]=[N:24][N:17]3[C:18]([C:20]([F:22])([F:23])[F:21])=[CH:19][C:14]([C:6]4[CH:7]=[CH:8][C:9]([C:10]([F:12])([F:11])[F:13])=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=4)=[N:15][C:16]=23)=[O:29])[CH:36]=[CH:35][CH:34]=1)(=[O:39])=[O:38])[CH3:42] | CCNS(=O)(=O)c1cccc(N)c1 | CCOc1cc(-c2cc(C(F)(F)F)n3ncc(C(=O)O)c3n2)ccc1C(F)(F)F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared from 5-(3-ethoxy-4-trifluoromethyl-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C.11) and 3-amino-N-ethyl-benzenesulfonamide [CAS 56445-08-0] according to general procedure II. Yellow solid. MS (ISP) 600.0 [(M−H)−]; mp 226° C. | CCNS(=O)(=O)c1cccc(NC(=O)c2cnn3c(C(F)(F)F)cc(-c4ccc(C(F)(F)F)c(OCC)c4)nc23)c1 | null | null | null |
222,302 | ord_dataset-42629b4cf1094978a5e5f29f22639ee7 | null | 1991-01-01T00:01:00 | true | C(O[C@H:5]1[C@H:10]([N:11]2[CH2:15][CH2:14][N:13]([CH3:16])[C:12]2=[N:17][C:18]#[N:19])[C:9]2[CH:20]=[C:21]([C:24]#[N:25])[CH:22]=[CH:23][C:8]=2[O:7][C:6]1([CH3:27])[CH3:26])(=O)C.N12CCCN=C1CCCCC2>C1(C)C=CC=CC=1>[C:18]([N:17]=[C:12]1[N:13]([CH3:16])[CH2:14][CH2:15][N:11]1[C:10]1[C:9]2[CH:20]=[C:21]([C:24]#[N:25])[CH:22]=[CH:23][C:8]=2[O:7][C:6]([CH3:27])([CH3:26])[CH:5]=1)#[N:19] | CC(=O)O[C@H]1[C@H](N2CCN(C)C2=NC#N)c2cc(C#N)ccc2OC1(C)C | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCC2=NCCCN2CC1 | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | 100 | 0.67 | To a suspension of trans-3-acetoxy-4-(2-cyanoimino-3-methylimidazolidin-1-yl)-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (0.45 g) in toluene (9 ml) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (0.23 ml), and the reaction mixture was stirred at 100° C. for 2 hours and 40 minutes. The solvent was removed under reduced pressure. The residue was poured into water (30 ml) and then extracted with ethyl acetate (45 ml). The organic layer was washed with brine (30 ml), dried over magnesium sulfate and evaporated in vacuo. The residue was recrystallized from ethanol to give 4-(2-cyanoimino-3-methylimidazolidin-1-yl)-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (0.27 g). | CN1CCN(C2=CC(C)(C)Oc3ccc(C#N)cc32)C1=NC#N | null | 71.7 | null |
1,256,216 | ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0 | null | 2013-01-01T00:02:00 | true | [NH:1]1[C:5]([C:6]2[CH:7]=[C:8]([C:12]3[C:13]([OH:18])=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:9]=[CH:10][CH:11]=2)=[N:4][N:3]=[N:2]1.[N+:19]([O-])([OH:21])=[O:20].O>C(O)C>[N+:19]([C:14]1[CH:15]=[CH:16][CH:17]=[C:12]([C:8]2[CH:9]=[CH:10][CH:11]=[C:6]([C:5]3[NH:1][N:2]=[N:3][N:4]=3)[CH:7]=2)[C:13]=1[OH:18])([O-:21])=[O:20] | Oc1ccccc1-c1cccc(-c2nnn[nH]2)c1 | O=[N+]([O-])O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CCO | null | null | null | null | null | null | null | null | null | null | 8 | 3′-(1H-Tetrazol-5-yl)-biphenyl-2-ol 8d (3.5 g, 14.7 mmol) was dissolved in 145 mL of ethanol under argon atmosphere. Fuming nitric acid (0.565 mL, 13.2 mmol) was added dropwise at 35° C. After the reaction mixture was reacted at room temperature for 1 hour, 150 mL of water was added. After standing overnight, the mixture was filtered. The filter cake was washed with 100 mL of water and dissolved in 500 mL of ethyl acetate and 250 mL of water. The separated organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The mixture was purified by silica gel column chromatography to obtain the title compound 3-nitro-3′-(1H-tetrazol-5-yl)-biphenyl-2-ol 8e (1 g, yield 27.0%) as a yellow solid. | O=[N+]([O-])c1cccc(-c2cccc(-c3nnn[nH]3)c2)c1O | null | 26.7 | null |
629,368 | ord_dataset-0a66204fc43e49c2922e6f9107e6b62f | null | 2004-01-01T00:03:00 | true | [CH:1]([C@H:4]1[O:9][CH2:8][C@H:7]([NH2:10])[CH2:6][O:5]1)([CH3:3])[CH3:2].Cl[C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]([CH2:22][C:23]2[CH:24]=[N:25][C:26]([OH:29])=[CH:27][CH:28]=2)=[CH:14][N:13]=1.C(N(CCCC)CCCC)CCC>CCOC(C)=O.C([O-])(O)=O.[Na+]>[CH:1]([C@H:4]1[O:9][CH2:8][C@H:7]([NH:10][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]([CH2:22][C:23]3[CH:24]=[N:25][C:26]([OH:29])=[CH:27][CH:28]=3)=[CH:14][N:13]=2)[CH2:6][O:5]1)([CH3:3])[CH3:2] | CC(C)[C@H]1OC[C@H](N)CO1 | Oc1ccc(Cc2cnc(Cl)c3ccccc23)cn1 | null | O=C([O-])O | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCCCN(CCCC)CCCC | CCOC(C)=O | null | null | null | null | null | null | null | null | null | null | null | In a sealed glass bottle under N2-atmosphere, 424 mg (2.92 mmol) of trans 2-isopropyl-[1,3]dioxan-5-ylamine, 396 mg (1.46 mmol) of 1-chloro-4-[(6-hydroxy-pyridin-3-yl)methyl]-isoquinoline (contains 1-iodo derivative) and 2 ml of tributylamine are stirred at 150° C. for 48 h. The resulting mixture is diluted with EtOAc and NaHCO3-solution, the aqueous layer is separated and extracted twice with EtOAc. The organic phases are washed with brine, dried (Na2SO4) and concentrated in vaccuo. “Reversed Phase” medium-pressure chromatography (water/acetonitrile/TFA) yields trans 1-(2-isopropyl-[1,3]dioxan-5-ylamino)-4-[(6-hydroxy-pyridin-3-yl)methyl]-isoquinoline; FAB-MS; (M+H)+=286; HPLC(gradient20-100) tRet=8.6. | CC(C)[C@H]1OC[C@H](Nc2ncc(Cc3ccc(O)nc3)c3ccccc23)CO1 | null | null | null |
165,227 | ord_dataset-12ef86aced0149e0917be82ce22190e2 | null | 1987-01-01T00:11:00 | true | [CH3:1][C:2]1[NH:3][C:4]([CH3:36])=[C:5]([C:32]([O:34][CH3:35])=[O:33])[CH:6]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([N+:29]([O-:31])=[O:30])[CH:24]=2)[C:7]=1[C:8]1[O:12][N:11]=[C:10]([CH2:13][S:14]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:15])[N:9]=1.ClC1C=C(C=CC=1)C(OO)=[O:42]>C(Cl)(Cl)Cl>[CH3:1][C:2]1[NH:3][C:4]([CH3:36])=[C:5]([C:32]([O:34][CH3:35])=[O:33])[CH:6]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([N+:29]([O-:31])=[O:30])[CH:24]=2)[C:7]=1[C:8]1[O:12][N:11]=[C:10]([CH2:13][S:14]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)(=[O:42])=[O:15])[N:9]=1 | O=C(OO)c1cccc(Cl)c1 | COC(=O)C1=C(C)NC(C)=C(c2nc(CS(=O)Cc3ccccc3)no2)C1c1cccc([N+](=O)[O-])c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClC(Cl)Cl | null | null | null | null | null | null | null | null | null | null | 25 | 8 | To a solution of 550 mg of methyl 1,4-dihydro-2,6-dimethyl-3-(3-benzylsulfinylmethyl-1,2,4-oxadiazol-5-yl)-4-(3-nitrophenyl)pyridine-5-carboxylate in 30 ml of chloroform was added 520 mg of m-chloroperoxybenzoic acid. After stirring at room temperature for 8 hours, the mixture was treated in the same manner as described in Example 117 to give 180 mg of methyl 1,4-dihydro-2,6-dimethyl-3-(3-benzylsulfonylmethyl-1,2,4-oxadiazol-5-yl)-4-(3-nitrophenyl)pyridine-5-carboxylate, m.p. 227° C. | COC(=O)C1=C(C)NC(C)=C(c2nc(CS(=O)(=O)Cc3ccccc3)no2)C1c1cccc([N+](=O)[O-])c1 | null | 31.7 | null |
1,247,833 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=3[Cl:20])[N:11]=[C:10]([C:21](O)=O)[C:9]=2[CH3:24])=[CH:4][CH:3]=1.[CH2:25]([NH:32][C:33]([CH3:38])([CH3:37])[C:34]([NH2:36])=[O:35])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>>[CH2:25]([N:32]1[C:33]([CH3:37])([CH3:38])[C:34](=[O:35])[N:36]=[C:21]1[C:10]1[C:9]([CH3:24])=[C:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[N:12]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=2[Cl:20])[N:11]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1 | Cc1c(C(=O)O)nn(-c2ccc(Cl)cc2Cl)c1-c1ccc(Cl)cc1 | CC(C)(NCc1ccccc1)C(N)=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Compound 13 was synthesized from 4a (250 mg, 0.66 mmol) and 5h (189 mg, 0.99 mmol) as a white solid (152 mg, 43%) in a manner similar to that described in Example 36. 1H NMR (400 MHz, CDCl3) δ 7.38 (d, 1H), 7.31 (d, 2H), 7.26 (m, 5H), 7.20 (dd, 1H), 7.04 (d, 2H), 7.01 (d, 1H), 5.29 (s, 2H), 2.45 (s, 3H), 1.31 (s, 6H); ESMS m/z: 537.1 (M+1). | Cc1c(C2=NC(=O)C(C)(C)N2Cc2ccccc2)nn(-c2ccc(Cl)cc2Cl)c1-c1ccc(Cl)cc1 | null | null | null |
562,209 | ord_dataset-7c28974b7fcf4c9c86d5f2a42ba328a2 | null | 2002-01-01T00:09:00 | true | [OH-].[Na+].O.[CH3:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9]1[CH2:14][C:15]3[C:20]([C:8]2=1)=[CH:19][CH:18]=[CH:17][CH:16]=3.[CH3:21]I>C1C=CC=CC=1>[CH3:21][N:10]1[C:11]2[C:7](=[CH:6][C:5]([CH3:4])=[CH:13][CH:12]=2)[C:8]2[C:20]3[C:15]([CH2:14][C:9]1=2)=[CH:16][CH:17]=[CH:18][CH:19]=3 | Cc1ccc2[nH]c3c(c2c1)-c1ccccc1C3 | CI | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | c1ccccc1 | null | null | null | null | null | null | null | null | null | 25 | 2 | 45 g of NaOH, 60 ml of water, 60 ml of benzene, 0.3 g of trimethyl-cethyl-ammonium bromide, 19.3(0.088 mol) of 2-methyl-5,6-dihydroindeno[2,1-b]indole, prepared in Example 8-bis, and 7.5 ml (0.12 mol) of CH3I were placed in a bulb. The resulting two-phase system was stirred for 2 hours at room temperature and then 10 minutes at reflux. Then the reaction mixture cooled to room temperature and filtered. The obtained precipitate was washed twice with ethanol and finally dried, thus obtaining 18 g of N-methyl-2-methyl-5,6-dihydroindeno[2,1-b]indole (yield=88%). | Cc1ccc2c(c1)c1c(n2C)Cc2ccccc2-1 | null | 88 | null |
1,347,633 | ord_dataset-6034127657614f02860ed057b62b882e | null | 2013-01-01T00:10:00 | true | Cl[C:2]1[C:7]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)=[O:9])=[C:6]([CH3:19])[CH:5]=[C:4]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[N:3]=1.[CH:26](/B(O)O)=[CH:27]\[CH3:28].CCO>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:18][C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][CH:15]=1)[CH2:11][NH:10][C:8]([C:7]1[C:2](/[CH:26]=[CH:27]/[CH3:28])=[N:3][C:4]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)=[CH:5][C:6]=1[CH3:19])=[O:9] | C/C=C/B(O)O | Cc1cc(N2CCOCC2)nc(Cl)c1C(=O)NCc1cccc(F)c1 | null | c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | CCO | null | null | null | null | null | null | null | null | null | 110 | null | To a solution of 400 mg (1.1 mmol) 2-chloro-N-[(3-fluorophenyl)-methyl]-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide in toluene (15 ml) were added 140 mg (1.7 mmol) (E)-prop-1-enylboronic acid, 1.1 g (3.3 mmol) CsCO3 and EtOH (1.5 ml). After degassing with argon for 15 min 370 mg (0.32 mmol) Pd(PPh3)4 were added and the RM was heated to 110° C. for 5 h. Subsequently the RM was filtered through celite and the filtrate was concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 3:1) provided 300 mg (0.8 mmol, 74%) (E)-N-(3-fluorobenzyl)-4-methyl-6-morpholino-2-(prop-1-enyl)-pyridine-3-carboxylic acid amide (example 9). [M+H]+ 370.2. | C/C=C/c1nc(N2CCOCC2)cc(C)c1C(=O)NCc1cccc(F)c1 | null | 72.7 | null |
1,397,211 | ord_dataset-12dc3bd21bcf44d09e5b4249afe15161 | null | 2014-01-01T00:02:00 | true | [F:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][N:11]=2)[C:5]([NH2:8])=[CH:6][CH:7]=1.[C:17]([O:21][C:22]([NH:24][C@@H:25]([CH3:29])[C:26](O)=[O:27])=[O:23])([CH3:20])([CH3:19])[CH3:18].C1C=NC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[C:17]([O:21][C:22](=[O:23])[NH:24][C@H:25]([C:26](=[O:27])[NH:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=1[NH:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][N:11]=1)[CH3:29])([CH3:18])([CH3:19])[CH3:20] | C[C@H](NC(=O)OC(C)(C)C)C(=O)O | Nc1ccc(F)cc1Nc1ccc(F)cn1 | null | CCN=C=NCCCN(C)C | Cl | On1nnc2cccnc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | null | null | null | null | null | null | null | null | null | null | 0 | 1 | A mixture of 4-fluoro-N2-(5-fluoropyridin-2-yl)benzene-1,2-diamine (30 mg, 0.136 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (28 mg, 0.15 mmol), HOAt (20 mg, 0.15 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (29 mg, 0.15 mmol) in DCM (5 mL) was stirred at 0° C. for 1 h. Additional (S)-2-tertbutoxycarbonylaminopropionic acid (5 mg), HOAt (4 mg) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (5 mg) were added and stirring continued for 30 min. The reaction mixture was partitioned between DCM and a saturated aqueous solution of NaHCO3. The organic layer was dried and concentrated in vacuo to afford {(S)-1-[4-fluoro-2-(5-fluoropyridin-2-ylamino)phenylcarbamoyl]ethyl}carbamic acid tert-butyl ester as an orange oil. LCMS (Method C): RT 3.51 min [M+H]+ 393.1. | C[C@H](NC(=O)OC(C)(C)C)C(=O)Nc1ccc(F)cc1Nc1ccc(F)cn1 | null | null | null |
1,436,657 | ord_dataset-275a3da8f45f4536ad29727f0ef9ba66 | null | 2014-01-01T00:06:00 | true | C(=O)([O-])[O-].[Cs+].[Cs+].[Br:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][CH:12]=[C:11]2[CH:17]=[O:18].I[CH:20]([CH3:22])[CH3:21]>CN(C=O)C>[Br:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[N:13]([CH:20]([CH3:22])[CH3:21])[CH:12]=[C:11]2[CH:17]=[O:18] | CC(C)I | O=Cc1c[nH]c2ccc(Br)cc12 | null | O=C([O-])[O-] | [Cs+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 25 | 0.25 | Cesium carbonate (545 mg, 1.67 mmol) was added to a stirred room temperature of 5-bromo-1H-indole-3-carbaldehyde (125 mg, 0.56 mmol) in DMF (1.0 mL) and the mixture was stirred at room temperature for 15 minutes. Then 2-iodopropane (0.112 mL, 1.116 mmol) was added and the solution was stirred at 80° C. for 2 hours. The solvent was removed under reduced pressure and the residue was partitioned between ethyl acetate (2×20 mL) and saturated sodium bicarbonate (5 mL), washed with brine (10 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to give the title compound (148 mg). | CC(C)n1cc(C=O)c2cc(Br)ccc21 | null | 99.3 | null |
822,085 | ord_dataset-ec58fad8331a42c5a67ad75aac6713b4 | null | 2008-01-01T00:05:00 | true | [C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@H:6]1[O:24][C:25]1[C:29]([CH2:30][C:31]2[CH:36]=[CH:35][C:34](/[CH:37]=[CH:38]/[CH2:39][C:40](O)=[O:41])=[CH:33][CH:32]=2)=[C:28]([CH:43]([CH3:45])[CH3:44])[NH:27][N:26]=1)(=[O:3])[CH3:2].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[NH2:68][C@@H:69]([CH3:80])[C:70]([O:72][CH2:73][C:74]1[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=1)=[O:71]>CN(C)C=O.O>[C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@H:6]1[O:24][C:25]1[C:29]([CH2:30][C:31]2[CH:32]=[CH:33][C:34](/[CH:37]=[CH:38]/[CH2:39][C:40](=[O:41])[NH:68][C@H:69]([C:70]([O:72][CH2:73][C:74]3[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=3)=[O:71])[CH3:80])=[CH:35][CH:36]=2)=[C:28]([CH:43]([CH3:45])[CH3:44])[NH:27][N:26]=1)(=[O:3])[CH3:2] | CC(=O)OC[C@H]1O[C@@H](Oc2n[nH]c(C(C)C)c2Cc2ccc(/C=C/CC(=O)O)cc2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O | C[C@H](N)C(=O)OCc1ccccc1 | null | CCN=C=NCCCN(C)C | Cl | On1nnc2ccccc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CN(C)C=O | null | null | null | null | null | null | null | null | null | 25 | 8 | To a solution of 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-({4-[(1E)-3-carboxyprop-1-enyl]phenyl}methyl)-5-isopropyl-1H-pyrazole (7.13 g) in N,N-dimethylformamide (30 mL) were added 1-hydroxybenzotriazole (2.31 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (3.25 g) and benzyl (S)-2-aminopropionate (8.34 g), and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate twice. The extracts were washed with water and brine successively, and dried over sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/2) to give 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-[(4-{(1E)-3-[(S)-1-(benzyloxycarbonyl)ethylcarbamoyl]prop-1-enyl}phenyl)methyl]-5-isopropyl-1H-pyrazole (3.25 g). This material was dissolved in methanol (40 mL). To the solution was added 10% palladium-carbon powder (1.0 g), and the mixture was stirred at room temperature under a hydrogen atmosphere overnight. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure to give 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-[(4-{3-[(S)-1-(carboxy)ethylcarbamoyl]propyl}phenyl)methyl]-5-isopropyl-1H-pyrazole (2.25 g). To a solution of the obtained 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-[(4-{3-[(S)-1-(carboxy)ethylcarbamoyl]propyl}phenyl)methyl]-5-isopropyl-1H-pyrazole (0.09 g) in N,N-dimethylformamide (0.5 mL) were added 1-hydroxybenzotriazole (0.026 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.037 g) and 2-amino-1,3-propanediol (0.12 g), and the mixture was stirred at room temperature for 1 hour. To the reaction mixture was added 5 mol/L aqueous sodium hydroxide solution (0.5 mL), and the mixture was stirred at room temperature for 1 hour. Acetic acid (0.3 mL) and water (1 mL) were added to the reaction mixture. The insoluble material was removed by filtration, and the filtrate was purified by preparative reverse phase column chromatography (Shiseido CAPCELL PAK UG120 ODS, 5 μL, 120 Å, 20×50 mm, flow rate 30 mL/minute linear gradient, water/acetonitrile=90/10-10/90) to give the title compound (0.017 g). | CC(=O)OC[C@H]1O[C@@H](Oc2n[nH]c(C(C)C)c2Cc2ccc(/C=C/CC(=O)N[C@@H](C)C(=O)OCc3ccccc3)cc2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O | null | 36.3 | null |
894,397 | ord_dataset-11068b1e475b4c5b82e56726ab0dddb7 | null | 2009-01-01T00:07:00 | true | [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[N:12]=[C:13]=[O:14].[NH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[C:26]3=[N:27][CH:28]=[CH:29][CH:30]=[C:25]3[NH:24][C:23]=2[C:31]([NH2:33])=[O:32])=[CH:18][CH:17]=1>O1CCCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[NH:12][C:13](=[O:14])[NH:15][C:16]1[CH:17]=[CH:18][C:19]([C:22]2[C:26]3=[N:27][CH:28]=[CH:29][CH:30]=[C:25]3[NH:24][C:23]=2[C:31]([NH2:33])=[O:32])=[CH:20][CH:21]=1 | NC(=O)c1[nH]c2cccnc2c1-c1ccc(N)cc1 | O=C=Nc1cc(C(F)(F)F)ccc1F | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1CCOC1 | null | null | null | null | null | null | null | null | null | null | null | 1 | 73 mg of 2-fluoro-5-trifluoromethylphenyl isocyanate are added to a solution of 80 mg of 3-(4-aminophenyl)-1H-pyrrolo[3,2-b]pyridine-2-carboxamide in 18 ml of tetrahydrofuran. After stirring for 1 hour, the mixture is concentrated under reduced pressure and the residue is purified by chromatography on a silica column, elution being carried out with a mixture of cyclohexane and ethyl acetate (20/80 by volume) to give 110 mg of 3-{4-[3-(2-fluoro-5-trifluoromethylphenyl)-ureido]phenyl}-1H-pyrrolo[3,2-b]pyridine-2-carboxamide, the characteristics of which are as follows: | NC(=O)c1[nH]c2cccnc2c1-c1ccc(NC(=O)Nc2cc(C(F)(F)F)ccc2F)cc1 | null | 75.8 | null |
1,386,616 | ord_dataset-31641fb65b34430fa7435229b949b604 | null | 2014-01-01T00:01:00 | true | [CH3:1][O:2][CH2:3][CH2:4][CH2:5][OH:6].[N+:7]([C:10]1[CH:17]=[CH:16][CH:15]=[C:14]([N+]([O-])=O)[C:11]=1[C:12]#[N:13])([O-:9])=[O:8]>>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][O:6][C:14]1[CH:15]=[CH:16][CH:17]=[C:10]([N+:7]([O-:9])=[O:8])[C:11]=1[C:12]#[N:13] | N#Cc1c([N+](=O)[O-])cccc1[N+](=O)[O-] | COCCCO | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Prepared as in Example 111c from 3-methoxypropan-1-ol and 2,6-dinitrobenzonitrile in 63.6% yield. 1H NMR (400 MHz, CDCl3) δ 2.16 (m, 2H), 3.36 (s, 3H), 3.63 (t, J=5.6 Hz, 2H), 4.29 (t, J=6.4 Hz, 2H), 7.35 (dd, J=8.8, 0.8 Hz, 1H), 7.69 (t, J=8.8 Hz, 1H), (dd, J=8.4, 0.8 Hz, 1H). | COCCCOc1cccc([N+](=O)[O-])c1C#N | null | 63.6 | null |
1,751,437 | ord_dataset-97eb2ab57fec4160922caae33b54d956 | null | 2016-01-01T00:08:00 | true | C[O:2][C:3]([C@@H:5]1[CH2:9][C@H:8]([NH:10][C:11]([C:13]2[CH:22]=[CH:21][C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]=2[OH:23])=[O:12])[CH2:7][N:6]1[CH2:24][CH:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1)=[O:4].[OH-].[Li+].Cl>CO>[CH:25]1([CH2:24][N:6]2[CH2:7][C@@H:8]([NH:10][C:11]([C:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[C:14]=3[OH:23])=[O:12])[CH2:9][C@H:5]2[C:3]([OH:4])=[O:2])[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1 | COC(=O)[C@@H]1C[C@H](NC(=O)c2ccc3ccccc3c2O)CN1CC1CCCCC1 | null | null | Cl | [Li+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | null | 24 | To a stirred solution of (2S,4S)-1-cyclohexylmethyl-4-[(1-hydroxy-naphthalene-2-carbonyl)-amino]-pyrrolidine-2-carboxylic acid methyl ester (350 mg, 0.85 mmol) in methanol (8 mL) was added lithium hydroxide (204 mg, 8.53 mmol) and the mixture was stirred at room temp. for 24 h. The reaction mixture was then acidified with dilute hydrochloric acid, extracted with ethyl acetate and washed with water and brine. The organic layer was dried over anhydrous sodium sulfate, filtered, concentrated and purified by column chromatography (using 15% EtOAc in hexane as eluent) to give (2S,4S)-1-cyclohexylmethyl-4-[(1-hydroxy-naphthalene-2-carbonyl)-amino]-pyrrolidine-2-carboxylic acid (250 mg, 74.0% yield) as a white solid. MS caled. for C23H29N2O4[(M+H)+] 397.0, obsd. 397.6. | O=C(N[C@H]1C[C@@H](C(=O)O)N(CC2CCCCC2)C1)c1ccc2ccccc2c1O | null | 74.2 | null |
484,003 | ord_dataset-cb5c1a9eddff4790b1bd650617c32d34 | null | 2000-01-01T00:11:00 | true | [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH:9]2[OH:21])=[CH:4][CH:3]=1.Br[CH2:23][C:24]1[CH:33]=[CH:32][C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:25]=1[O:34][CH3:35]>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15])[CH2:10][CH:9]2[O:21][CH2:23][C:24]2[CH:33]=[CH:32][C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:25]=2[O:34][CH3:35])=[CH:6][CH:7]=1 | CC(C)(C)OC(=O)N1CCC(c2ccc(F)cc2)C(O)C1 | COc1c(CBr)ccc2ccccc12 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | In an analogous manner to that described in Example 3(c), by alkylating tert-butyl (3RS,4RS)-4-(4-fluorophenyl)-3-hydroxy-piperidine-1-carboxylate [Example 3(b)] with 2-bromomethyl-1-methoxy-naphthalene there was obtained tert-butyl (3RS,4RS)-4-(4-fluorophenyl)-3-[1-methoxy-naphthalen-2-yl-methoxy]-piperidine-1-carboxylate as a colourless resin; MS: 465 (M)+. | COc1c(COC2CN(C(=O)OC(C)(C)C)CCC2c2ccc(F)cc2)ccc2ccccc12 | null | null | null |
182,918 | ord_dataset-f25e1b7f8ef54305a5170f5395a768c7 | null | 1989-01-01T00:01:00 | true | [CH3:1][C:2]1[NH:3][C:4](=[O:22])[CH2:5][S:6][C:7]=1[CH:8]1[CH:13]=[CH:12][N:11](C(OCC(Cl)(Cl)Cl)=O)[N:10]=[CH:9]1.[S]>>[CH3:1][C:2]1[NH:3][C:4](=[O:22])[CH2:5][S:6][C:7]=1[C:8]1[CH:13]=[CH:12][N:11]=[N:10][CH:9]=1 | CC1=C(C2C=CN(C(=O)OCC(Cl)(Cl)Cl)N=C2)SCC(=O)N1 | null | null | [S] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 140 | 1.5 | 5-methyl-6-[1-(2,2,2-trichloroethoxycarbonyl)-1,4-dihydro-4-pyridazinyl]-2H-1,4-thiazin-3(4H)-one (2.4 g) was well mixed with sulfur sublimed (10.7 g) in a mortar and the mixture was stirred at 140° C. for 1.5 hours and then was cooled to ambient temperature. The obtained solid was ground and was extracted with methanol. Methanol was removed under reduced pressure. The residue was dissolved in 50 ml of 2N hydrochloric acid. The insoluble matter was removed by filtration and the filtrate was adjusted to pH 7.2 by 2N aqueous sodium hydroxide. The resulting precipitates were removed by filtration. The filtrate was extracted with chloroform (20 ml×5 times) and the extract was evaporated to dryness. After combined with the above solid, the residue was recrystallized from methanol to give the titled compound (0.3 g, yield 23%) as pale yellow plates. | CC1=C(c2ccnnc2)SCC(=O)N1 | null | 23.2 | null |
1,664,052 | ord_dataset-42cd9bc5aae3485f9a58f1527bd3abf0 | null | 2015-01-01T00:11:00 | true | Br[C:2]1[C:10]2[CH:11]=[C:12]3[C:20]([C:21]([CH3:23])([CH3:22])[C:9]=2[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH:7]=2)=[C:19]1[C:14]([CH:15]=[CH:16][CH:17]=[CH:18]1)=[N:13]3.[C:30]1(C2C=CC=CC=2)[CH:35]=[CH:34][C:33]([N:36](C2C=CC(B3OC(C)(C)C(C)(C)O3)=CC=2)[C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[CH:32][CH:31]=1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1.C(O)C>[C:6]1([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:7]=[CH:8][C:3]([N:36]([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[C:33]2[CH:32]=[CH:31][C:30]([C:2]3[C:10]4[CH:11]=[C:12]5[C:20]([C:21]([CH3:23])([CH3:22])[C:9]=4[C:8]4[C:3]=3[CH:4]=[CH:5][CH:6]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH:7]=4)=[C:19]3[C:14]([CH:15]=[CH:16][CH:17]=[CH:18]3)=[N:13]5)=[CH:35][CH:34]=2)=[CH:4][CH:5]=1 | CC1(C)OB(c2ccc(N(c3ccccc3)c3ccc(-c4ccccc4)cc3)cc2)OC1(C)C | CC1(C)C2=C(C=C3N=c4ccccc4=C31)C(Br)=C1C=CC(c3ccccc3)C=C12 | null | c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1 | O=C([O-])[O-] | [K+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | 73 | 8 | 7-Bromo-12,12-dimethyl-10-phenyl-10,12-dihydro-indeno[2,1-b]carbazole synthesized in Example 1 (3.0 g), (biphenyl-4-yl)-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]-phenylamine (3.7 g), a toluene/ethanol (4/1, v/v) mixed solvent (50 ml), and a 2M potassium carbonate aqueous solution (10 ml) were added to a nitrogen-substituted reaction vessel and aerated with nitrogen gas for 30 min under ultrasonic irradiation. The mixture was heated after adding tetrakis(triphenylphosphine)palladium (0.4 g), and stirred at 73° C. for 8 hours. After the mixture was cooled to a room temperature, a precipitated crude product was collected by filtration. 1,2-Dichlorobenzene (140 ml) was added to the crude product, and the crude product was dissolved while being heated, and after removing insoluble matter by filtration, a filtrate was concentrated under reduced pressure. Purification by recrystallization using 1,2-dichlorobenzene (100 ml) was performed to obtain a white powder of 7-[4-{(biphenyl-4-yl)-phenylamino}-phenyl]-12,12-dimethyl-10-phenyl-10,12-dihydroindeno[2,1-b]carbazole (2.7 g; yield 57.8%). | CC1(C)C2=C(C=C3N=c4ccccc4=C31)C(c1ccc(N(c3ccccc3)c3ccc(-c4ccccc4)cc3)cc1)=C1C=CC(c3ccccc3)C=C12 | null | 116.2 | null |
1,769,416 | ord_dataset-0b32b90cc77b4a3db47ad263e0bbc1a8 | null | 2016-01-01T00:09:00 | true | Cl[CH2:2][C:3]1[C:4]([S:10][CH:11]2[CH2:15][CH2:14][CH2:13]C2)=[N:5][C:6](C)=[CH:7][CH:8]=1.C([O:18][C:19]([CH:21]1[CH2:23][CH:22]1[C:24]1[CH:29]=[C:28]([F:30])[C:27]([OH:31])=[C:26]([F:32])[CH:25]=1)=[O:20])C>>[CH:11]1([S:10][C:4]2[C:3]([CH2:2][O:31][C:27]3[C:26]([F:32])=[CH:25][C:24]([CH:22]4[CH2:23][CH:21]4[C:19]([OH:20])=[O:18])=[CH:29][C:28]=3[F:30])=[CH:8][CH:7]=[CH:6][N:5]=2)[CH2:15][CH2:14][CH2:13]1 | CCOC(=O)C1CC1c1cc(F)c(O)c(F)c1 | Cc1ccc(CCl)c(SC2CCCC2)n1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 3-Chloromethyl-2-cyclobutylsulfanyl-pyridine (0.024 g, 0.113 mmol) obtained in Step C of Preparation Example 23 and 2-(3,5-difluoro-4-hydroxy-phenyl)-cyclopropane carboxylic acid ethyl ester (0.026 g, 0.113 mmol) obtained in Step B of Preparation Example 31 were used to react sequentially in the same manner as in Steps A and B of Example 1 to obtain the title compound (0.036 g, 81%). | O=C(O)C1CC1c1cc(F)c(OCc2cccnc2SC2CCC2)c(F)c1 | null | 81.4 | null |
1,460,022 | ord_dataset-a86112d52cd54525a5e36d41f18aced2 | null | 2014-01-01T00:07:00 | true | COC1C=CC(C[N:8]2[C:12]3=[N:13][CH:14]=[C:15]([C:17]4[CH:18]=[C:19]([NH:23][C:24](=[O:26])[CH3:25])[CH:20]=[CH:21][CH:22]=4)[CH:16]=[C:11]3[C:10]([CH3:27])=[N:9]2)=CC=1.FC(F)(F)C(O)=O>C(Cl)(Cl)Cl>[CH3:27][C:10]1[C:11]2[C:12](=[N:13][CH:14]=[C:15]([C:17]3[CH:18]=[C:19]([NH:23][C:24](=[O:26])[CH3:25])[CH:20]=[CH:21][CH:22]=3)[CH:16]=2)[NH:8][N:9]=1 | COc1ccc(Cn2nc(C)c3cc(-c4cccc(NC(C)=O)c4)cnc32)cc1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClC(Cl)Cl | O=C(O)C(F)(F)F | null | null | null | null | null | null | null | null | null | 50 | null | To a solution of N-(3-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)phenyl)acetamide (113) (50 mg, 0.129 mmol) dissolved in chloroform (10 mL) was added trifluoroacetic acid (5 mL) and the reaction mixture was heated at 50° C. for 12 h. After completion of the reaction the solvents were removed and diluted with cold water, pH was adjusted to 8 and the aqueous phase extracted with chloroform two times. The organic layer was washed with brine solution and dried over sodium sulphate and the solvents were removed. The crude was passed through 100-200 mesh silica gel eluting the compound at 40% ethyl acetate in hexane as pale yellow solid N-(3-(3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)phenyl)acetamide 114 (30 mg). MS m/z 266.9 (M+H)+. | CC(=O)Nc1cccc(-c2cnc3[nH]nc(C)c3c2)c1 | null | null | null |
1,657,670 | ord_dataset-42cd9bc5aae3485f9a58f1527bd3abf0 | null | 2015-01-01T00:11:00 | true | C([O:8][C:9]1[CH:10]=[C:11]([C:15]2[CH:16]=[C:17]3[C:22](=[N:23][CH:24]=2)[N:21]([C:25]([NH2:27])=[O:26])[CH2:20][CH2:19][CH2:18]3)[CH:12]=[N:13][CH:14]=1)C1C=CC=CC=1>CCO.[Pd]>[OH:8][C:9]1[CH:10]=[C:11]([C:15]2[CH:16]=[C:17]3[C:22](=[N:23][CH:24]=2)[N:21]([C:25]([NH2:27])=[O:26])[CH2:20][CH2:19][CH2:18]3)[CH:12]=[N:13][CH:14]=1 | NC(=O)N1CCCc2cc(-c3cncc(OCc4ccccc4)c3)cnc21 | null | null | [Pd] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | null | null | A stirred suspension of 6-(5-benzyloxy-pyridin-3-yl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid amide (167 mg, 0.46 mmol) in EtOH (10 mL) is hydrogenated over 10% palladium on carbon (17 mg) under balloon pressure for 16 h. The catalyst is removed by filtration through diatomaceous earth, washing well with DCM. The solvent is evaporated to afford the title compound (125 mg). | NC(=O)N1CCCc2cc(-c3cncc(O)c3)cnc21 | null | 100.5 | null |
1,235,159 | ord_dataset-e96f5a2842f14e5380461c234100f05a | null | 2012-01-01T00:12:00 | true | C(O)C.[O:4]1[C:9]2[CH:10]=[CH:11][C:12]([CH2:14][NH:15][CH:16]3[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][N:24]4[C:33]5[C:28](=[CH:29][CH:30]=[C:31]([O:34][CH3:35])[CH:32]=5)[C:27](/[CH:36]=[CH:37]/[C:38]([O:40]CC)=[O:39])=[CH:26][C:25]4=[O:43])[CH2:18][CH2:17]3)=[CH:13][C:8]=2[O:7][CH2:6][CH2:5]1.[OH-].[Na+]>O>[O:4]1[C:9]2[CH:10]=[CH:11][C:12]([CH2:14][NH:15][CH:16]3[CH2:17][CH2:18][N:19]([CH2:22][CH2:23][N:24]4[C:33]5[C:28](=[CH:29][CH:30]=[C:31]([O:34][CH3:35])[CH:32]=5)[C:27](/[CH:36]=[CH:37]/[C:38]([OH:40])=[O:39])=[CH:26][C:25]4=[O:43])[CH2:20][CH2:21]3)=[CH:13][C:8]=2[O:7][CH2:6][CH2:5]1 | CCOC(=O)/C=C/c1cc(=O)n(CCN2CCC(NCc3ccc4c(c3)OCCO4)CC2)c2cc(OC)ccc12 | null | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | O | null | null | null | null | null | null | null | null | null | null | 1 | To 1 mL of an ethanol solution containing 65 mg of ethyl(2E)-3-(1-(2-(4-((2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino)piperidin-1-yl)ethyl)-7-methoxy-2-oxo-1,2-dihydroquinolin-4-yl)acrylate, 0.2 mL of water and 0.11 mL of 5 mol/L aqueous sodium hydroxide solution were added and stirred for 1 hour. 2 mL of water was added, removed ethanol under reduced pressure, adjusted to pH 6.0 with 1 mol/L hydrochloric acid, and the resulting solid was filtered to afford 48 mg of (2E)-3-(1-(2-(4-((2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino)piperidin-1-yl)ethyl)-7-methoxy-2-oxo-1,2-dihydroquinolin-4-yl)acrylic acid as a yellow solid. | COc1ccc2c(/C=C/C(=O)O)cc(=O)n(CCN3CCC(NCc4ccc5c(c4)OCCO5)CC3)c2c1 | null | 77.8 | null |
1,523,287 | ord_dataset-8c74302143c04eb9983e4b3a7ead2d72 | null | 2014-01-01T00:12:00 | true | CN(/[CH:4]=[C:5]1\[CH2:6][CH2:7][CH2:8][C:9]2[C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[N:12][N:11]([CH3:19])[C:10]=2[C:20]\1=O)C.C(=O)(O)O.[NH2:26][C:27]([NH2:29])=[NH:28]>CCO>[NH2:28][C:27]1[N:29]=[C:20]2[C:10]3[N:11]([CH3:19])[N:12]=[C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:9]=3[CH2:8][CH2:7][CH2:6][C:5]2=[CH:4][N:26]=1 | CCOC(=O)c1nn(C)c2c1CCC/C(=C\N(C)C)C2=O | N=C(N)N | null | O=C(O)O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | null | null | To a solution of ethyl (7E)-7-[(dimethylamino)methylidene]-1-methyl-8-oxo-1,4,5,6,7,8-hexahydrocyclohepta[c]pyrazole-3-carboxylate (240 mg, 0.86 mmol) in EtOH (7.5 mL), guanidine carbonate (86 mg, 0.47 mmol) was added. The reaction mixture was stirred under reflux for 24 h. The solvent was removed under reduced pressure, the crude was triturated with hexane and EtOH and collected by filtration to give 84 mg of a white solid (79% yield). | CCOC(=O)c1nn(C)c2c1CCCc1cnc(N)nc1-2 | null | 62.2 | null |
1,528,351 | ord_dataset-8c74302143c04eb9983e4b3a7ead2d72 | null | 2014-01-01T00:12:00 | true | C[O:2][C:3](=O)[CH:4]=[CH:5][C:6](=[C:11]([NH:13][CH2:14][CH:15]1[CH2:19][CH2:18][CH2:17][CH2:16]1)[CH3:12])[C:7]([O:9][CH3:10])=[O:8].C[O-].[Na+].[Br:24]N1C(=O)CCC1=O>CO>[CH3:10][O:9][C:7]([C:6]1[CH:5]=[C:4]([Br:24])[C:3](=[O:2])[N:13]([CH2:14][CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[C:11]=1[CH3:12])=[O:8] | COC(=O)C=CC(C(=O)OC)=C(C)NCC1CCCC1 | O=C1CCC(=O)N1Br | null | C[O-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | 25 | null | MeOH (240 mL) was added to a flask containing 4-[1-(cyclopentylmethyl-amino)-ethylidene]-pent-2-enedioic acid dimethyl ester (7.2 g, 25.6 mmol). NaOMe solution (5.9 mL, 25.6 mmol, 4.375 M in MeOH) and N-bromosuccinimide (5.5 g, 30.7 mmol) were added, and the resulting mixture was refluxed for 1 h. After cooling to r.t., the solvent was evaporated in vacuo. Saturated NH4Cl was added, and the resulting mixture was extracted with CH2Cl2. The organic layer was dried over MgSO4 and concentrated. The crude product was chromatographed (0-25% EtOAc/hexanes) to give 4.46 g of the title compound. MS: (+) m/z 350.22, 352.24 (M+Na, 79/81Br). | COC(=O)c1cc(Br)c(=O)n(CC2CCCC2)c1C | null | 53.1 | null |
698,727 | ord_dataset-4e9c2fa02a7544fd839206719263345f | null | 2006-01-01T00:02:00 | true | [N+:1]([C:4]1[CH:25]=[CH:24][C:7]([CH2:8][O:9][C:10](=[O:23])[CH2:11][N:12](C(OC(C)(C)C)=O)[CH:13]([CH3:15])[CH3:14])=[CH:6][CH:5]=1)([O-:3])=[O:2].[ClH:26].C(OCC)C>O1CCOCC1>[ClH:26].[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:8][O:9][C:10](=[O:23])[CH2:11][NH:12][CH:13]([CH3:14])[CH3:15])=[CH:24][CH:25]=1)([O-:3])=[O:2] | CC(C)N(CC(=O)OCc1ccc([N+](=O)[O-])cc1)C(=O)OC(C)(C)C | null | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCOCC | C1COCCO1 | null | null | null | null | null | null | null | null | null | 25 | 8 | To a solution of (N-t-butoxycarbonyl-N-isopropyl-amino)-acetic acid p-nitrobenzyl ester (1.93 g, 5.48 mmol) in 1,4-dioxane (20 ml) was added a solution of 4N hydrogen chloride in 1,4-dioxane (20 ml) in an ice bath, and the mixture was stirred at room temperature overnight. After checking the completion of the reaction, diethyl ether was added thereto the reaction mixture was stirred for 30 minutes and filtered, and the obtained residue was washed with diethyl ether and dried to give (isopropylamino)acetic acid p-nitrobenzyl ester hydrochloride (1.50 g, yield 95%) as white crystals. | CC(C)NCC(=O)OCc1ccc([N+](=O)[O-])cc1 | null | 95 | null |
214,238 | ord_dataset-b67d30cd146f49dcbf24faee022f1a09 | null | 1990-01-01T00:08:00 | true | [NH2:1][C:2]1[N:3]([CH3:13])[C:4]2[C:9]([C:10]=1[C:11]#[N:12])=[CH:8][CH:7]=[CH:6][CH:5]=2.[C:14]([O:20][CH2:21][CH3:22])(=[O:19])[CH2:15][C:16]([CH3:18])=O>>[NH2:12][C:11]1[C:10]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]([CH3:13])[C:2]=2[N:1]=[C:16]([CH3:18])[C:15]=1[C:14]([O:20][CH2:21][CH3:22])=[O:19] | CCOC(=O)CC(C)=O | Cn1c(N)c(C#N)c2ccccc21 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared from 2-amino-1-methyl-1H-indole-3-carbonitrile (D22) and ethyl acetoacetate using a method similar to that described in Description 2. | CCOC(=O)c1c(C)nc2c(c1N)c1ccccc1n2C | null | null | null |
1,128,357 | ord_dataset-285df12e34cd46e993e3c8ebc3a8962a | null | 2012-01-01T00:01:00 | true | Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][F:9])[N:3]=1.[C:10]([O:14][C:15](=[O:31])[N:16]([C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=1[CH3:30])[C:17](=[O:22])[CH2:18][CH2:19][C:20]#[CH:21])([CH3:13])([CH3:12])[CH3:11]>>[C:10]([O:14][C:15](=[O:31])[N:16]([C:17](=[O:22])[CH2:18][CH2:19][C:20]#[C:21][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][F:9])[N:3]=1)[C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=1[CH3:30])([CH3:13])([CH3:11])[CH3:12] | C#CCCC(=O)N(C(=O)OC(C)(C)C)c1ccc(F)cc1C | FCc1cccc(Br)n1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | The title compound was prepared in accordance with the general method of Example 1, from 2-bromo-6-(fluoromethyl)pyridine (150 mg, 0.79 nm mmol, Example 190(E)) and (4-fluoro-2-methyl-phenyl)-pent-4-ynoyl-carbamic acid tert-butyl ester (241 mg, 0.79 mmol, 188(B)). Reaction time: 3 hours. The crude residue was purified by flash chromatography (cyclohexane/AcOEt 4:1) to yield 260 mg (0.63 mmol, 790%) of [5-(6-fluoromethyl-pyridin-2-yl)-pent-4-ynoyl]-(4-fluoro-2-methyl-phenyl)-carbamic acid tert-butyl ester as a white solid. | Cc1cc(F)ccc1N(C(=O)CCC#Cc1cccc(CF)n1)C(=O)OC(C)(C)C | null | 79.8 | null |
243,469 | ord_dataset-fa3b512e2d924b9b965301ebcba6853d | null | 1992-01-01T00:03:00 | true | [CH:1]1([NH:4][C:5]2[N:10]=[C:9]([N:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:13][CH2:12]3)[C:8]([F:22])=[CH:7][CH:6]=2)[CH2:3][CH2:2]1.[CH2:23]([O:25][C:26](=[O:37])[C:27](=[CH:33]OCC)[C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH3:24]>C1(C)C(C)=CC=CC=1>[CH:1]1([N:4]([CH:33]=[C:27]([C:26]([O:25][CH2:23][CH3:24])=[O:37])[C:28]([O:30][CH2:31][CH3:32])=[O:29])[C:5]2[CH:6]=[CH:7][C:8]([F:22])=[C:9]([N:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:13][CH2:12]3)[N:10]=2)[CH2:2][CH2:3]1 | CCOC(=O)N1CCN(c2nc(NC3CC3)ccc2F)CC1 | CCOC=C(C(=O)OCC)C(=O)OCC | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1C | null | null | null | null | null | null | null | null | null | null | null | null | A solution of 3.8 g (12.3 mmole) of 4-[6-(cyclopropylamino)-3-fluoro-2-pyridinyl]-1-piperazine carboxylic acid, ethyl ester, 2.7 g (12.3 mmole) of diethyl(ethoxymethylene)malonate and 50 ml of xylene was refluxed for 24 hours. The solvent was removed in vacuo and the residue was chromatographed over silica gel eluting with chloroform/ethyl acetate (80/20) to give 2.3 g of the title compound as a viscous oil which was used without further purification. | CCOC(=O)C(=CN(c1ccc(F)c(N2CCN(C(=O)OCC)CC2)n1)C1CC1)C(=O)OCC | null | 39.1 | null |
530,083 | ord_dataset-f027aa93238e424fbbf9bad1c7699adc | null | 2001-01-01T00:12:00 | true | [Cl:1][C:2]1[CH:11]=[C:10]([C:12]([NH:14][CH2:15][C:16]2[C:24]3[N:23]=[CH:22][N:21](C(OC(C)(C)C)=O)[C:20]=3[CH:19]=[CH:18][CH:17]=2)=[O:13])[CH:9]=[CH:8][C:3]=1[C:4]([O:6]C)=[O:5]>CO.[OH-].[Li+]>[Cl:1][C:2]1[CH:11]=[C:10]([C:12]([NH:14][CH2:15][C:16]2[C:24]3[NH:23][CH:22]=[N:21][C:20]=3[CH:19]=[CH:18][CH:17]=2)=[O:13])[CH:9]=[CH:8][C:3]=1[C:4]([OH:6])=[O:5] | COC(=O)c1ccc(C(=O)NCc2cccc3c2ncn3C(=O)OC(C)(C)C)cc1Cl | null | null | [Li+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | null | null | A mixture of 4-(azidomethyl)benzimidazole-1-carboxylic acid, 1,1-dimethylethyl ester (Example 13; 1.40, 5.1 mmol), 1-[[3-chloro-4-(methoxycarbonyl)benzoyl]oxy]-2,5-pyrrolidinedione (Example 5; 1.62 g, 5.2 mmol), and 10% palladium on charcoal (210 mg) in methanol (40 mL) and benzene (2 mL) was hydrogenated at atmospheric pressure for 105 min and then filtered through Celite. Tlc indicated that the reaction was not complete so more 10% palladium on charcoal (210 mg) was added and the mixture was hydrogenated at atmospheric pressure for 3 h and then shaken at 50 psi of hydrogen for 3 h. The reaction mixture was allowed to stand under hydrogen for 12 h, then filtered through Celite, evaporated, and chromatographed (20-100% ethyl acetate/hexanes) to give 2-chloro-4-[[[[1-[(1,1-dimethylethoxy)carbonyl]benzimidazol-4-yl]methyl]amino]carbonyl]benzoic acid, methyl ester (1.50 g, 66%). A solution of the ester (1.45 g, 3.3 mmol) in methanol (15 mL) and 3 M lithium hydroxide solution (5.5 mL) was stirred at room temperature overnight. A white solid was filtered off and discarded. The filtrate was evaporated to dryness. Water and 1 M HCl (16.6 mL) were added, and the mixture was filtered and washed with water to give 2-chloro-4-[[[(benzimidazol-4-yl)methyl]amino]carbonyl]-benzoic acid (925 mg, 86%). | O=C(NCc1cccc2nc[nH]c12)c1ccc(C(=O)O)c(Cl)c1 | null | 85 | null |
595,913 | ord_dataset-843ef38b45484f72826f5f39d8a29c4d | null | 2003-01-01T00:06:00 | true | [C:1]([CH:4]([CH2:9][CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:5]([O:7]C)=[O:6])(=[O:3])[CH3:2].[OH-].[Na+]>O1CCOCC1>[C:1]([CH:4]([CH2:9][CH2:10][CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[C:5]([OH:7])=[O:6])(=[O:3])[CH3:2] | COC(=O)C(CCCc1ccccc1)C(C)=O | null | null | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | C1COCCO1 | null | null | null | null | null | null | null | null | null | null | 0 | null | 1.00 g (4.45 mmol) of methyl 2-acetyl-5-phenylpentanoate is dissolved in 10 ml of dioxane and cooled to 0° C. 8.5 ml of a 1 M sodium hydroxide solution are added with cooling. After a reaction time of 5 h, the batch is concentrated, treated with 10 ml of ethyl acetate and 10 ml of water and extracted by shaking. The water phase is recovered, cooled to 0° C. and slowly treated with 1 N hydrochloric acid with cooling until pH 1 is reached. It is then extracted with dichloromethane. The dichloromethane phase is dried and directly reacted further without concentrating. | CC(=O)C(CCCc1ccccc1)C(=O)O | null | null | null |
52,472 | ord_dataset-3d470a6df4a04b1996e024a38c53e818 | null | 1979-01-01T00:03:00 | true | [Br:1][C:2]1[CH:3]=[C:4]([CH:11]=[CH:12][CH:13]=1)[C:5]([N:8]=[C:9]=[O:10])([CH3:7])[CH3:6].[C-]#N.[CH3:16][NH:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[Br:1][C:2]1[CH:3]=[C:4]([CH:11]=[CH:12][CH:13]=1)[C:5]([NH:8][C:9](=[O:10])[N:17]([CH3:16])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)([CH3:7])[CH3:6] | CC(C)(N=C=O)c1cccc(Br)c1 | CNc1ccccc1 | null | [C-]#N | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | 60 | null | 2.4 g of m-bromo-α,α-dimethylbenzyl isocyanate, prepared from the corresponding cyanide in the same way as in Synthesis Example 1, was added to 1.1 g of N-methylaniline and the mixture was heated at 60° C. for 2 hours. After allowing the reaction mixture to cool, the precipitated white crystals were separated by filtration and washed with n-hexane to obtain 3.0 g of the title compound. | CN(C(=O)NC(C)(C)c1cccc(Br)c1)c1ccccc1 | null | 86.4 | null |
538,175 | ord_dataset-1884c7bf3d544afdb8d17b5d41b90a27 | null | 2002-01-01T00:03:00 | true | [CH:1]([N:4]([CH2:8][C:9]1[CH:41]=[CH:40][C:12]([C:13]([CH:15]2[CH2:20][CH2:19][N:18](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[CH2:17][CH2:16]2)=[O:14])=[CH:11][CH:10]=1)[CH:5]([CH3:7])[CH3:6])([CH3:3])[CH3:2]>C(O)(=O)C>[CH:1]([N:4]([CH2:8][C:9]1[CH:10]=[CH:11][C:12]([C:13]([CH:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)=[O:14])=[CH:40][CH:41]=1)[CH:5]([CH3:7])[CH3:6])([CH3:2])[CH3:3] | CC(C)N(Cc1ccc(C(=O)C2CCN(C(c3ccccc3)(c3ccccc3)c3ccccc3)CC2)cc1)C(C)C | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CC(=O)O | null | null | null | null | null | null | null | null | null | null | 80 | 1 | A mixture of 4-(4-diisopropylaminomethylbenzoyl)-1-tritylpiperidine (1.3 g) and 80% acetic acid aqueous solution (20 ml) was stirred at 80° C. for 1 hour and concentrated. To the residue was added water, and the solution was extracted with ethyl acetate. The extract was washed with water, dried (MgSO4) and concentrated to give an oil of 4-(4-diisopropylaminomethylbenzoyl)piperidine (1.0 g). To a solution of the oil (302 mg) in THF (10 ml) was added 6-chloronaphthalene-2-sulfonylchloride (261 mg), and the mixture was stirred at room temperature for 1 hour. To the mixture was added sodium hydrogen carbonate aqueous solution, and the mixture was extracted with ethyl acetate. The extract was washed with water, dried (MgSO4) and concentrated. The residue was subjected to silica gel chromatography and eluted with hexane-ethyl acetate (4:1) to give the title compound (0.15g). | CC(C)N(Cc1ccc(C(=O)C2CCNCC2)cc1)C(C)C | null | 138.6 | null |
1,240,449 | ord_dataset-c544c0c663f54dbea4ddb52ddde7934e | null | 2013-01-01T00:01:00 | true | [F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=O.C(O)(=O)[CH2:11][C:12]([OH:14])=[O:13].N1CCCCC1.N1C=CC=CC=1.Cl>>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[CH:11][C:12]([OH:14])=[O:13] | O=Cc1cccc(F)c1 | O=C(O)CC(=O)O | null | Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | c1ccncc1 | C1CCNCC1 | null | null | null | null | null | null | null | null | null | 25 | 1 | 5 g (40.1 mmol) of 3-fluoro benzaldehyde, 8.38 g (2 eq.) of malonic acid, and 0.34 g (0.1 eq.) of piperidine were added to 9.52 g (3 eq.) of pyridine and stirred at room temperature for about 1 hour. After heating it to 80° C., the mixture was stirred for 12 hours. After the reaction, the resulting solution cooled to room temperature and was slowly added with 1M HCl until it was titrated to about pH 4. The resulting powder was filtered and washed with water, and then dried in a vacuum oven. (Yield: 84%) | O=C(O)C=Cc1cccc(F)c1 | null | 84 | null |
1,066,181 | ord_dataset-ffbef48837674f39816de887b5dc8bae | null | 2011-01-01T00:06:00 | true | [CH3:1][C@@:2]1([C:8]([OH:10])=O)[CH2:6][O:5][C:4](=[O:7])[O:3]1.C(Cl)(=O)C([Cl:14])=O.CN(C=O)C>ClCCl>[CH3:1][C@@:2]1([C:8]([Cl:14])=[O:10])[CH2:6][O:5][C:4](=[O:7])[O:3]1 | C[C@@]1(C(=O)O)COC(=O)O1 | O=C(Cl)C(=O)Cl | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | CN(C)C=O | null | null | null | null | null | null | null | null | null | 25 | 0.17 | To a solution of the compound prepared in Example 184 (330 mg) in dichloromethane (11 mL) were added oxalyl chloride (290 μL) and DMF (0.1 mL) and the reaction mixture was stirred at room temperature for 10 minutes. The reaction mixture was concentrated in vacuum condition to give the title compound (2.0 g) having the following physical data as a coarse product. This compound was used for the next reaction without being purified. | C[C@@]1(C(=O)Cl)COC(=O)O1 | null | null | null |
724,123 | ord_dataset-0387783899c642a8b7eb4ba379bcdf5d | null | 2006-01-01T00:08:00 | true | [Br:1][C:2]1[S:6][C:5]([C:7](=[O:9])C)=[C:4]([CH3:10])[CH:3]=1.[BH4-].[Na+].Cl>C(O)C>[Br:1][C:2]1[S:6][C:5]([CH2:7][OH:9])=[C:4]([CH3:10])[CH:3]=1 | CC(=O)c1sc(Br)cc1C | null | null | Cl | [BH4-] | [Na+] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CCO | null | null | null | null | null | null | null | null | null | null | 0 | 1 | A mixture of 1-(5-bromo-3-methylthien-2-yl)ethanone (intermediate 82, 5.13 g) in ethanol (50 ml) was treated with sodium borohydride (0.947 g). The reaction was stirred at 0° C. for 60 minutes and warmed to room temp for 30 minutes. 2M Aqueous hydrochloric acid was added and the reaction mixture was extracted with ethyl acetate twice. The organic solutions were combined and dried with brine and over magnesium sulfate. The title compound was isolated after removal of the desiccant and evaporation of the solvent. | Cc1cc(Br)sc1CO | null | null | null |
1,391,012 | ord_dataset-31641fb65b34430fa7435229b949b604 | null | 2014-01-01T00:01:00 | true | [CH3:1][C:2]1[CH:6]=[C:5]([NH2:7])[N:4]([CH:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)[N:3]=1.[CH:15]1([C:18](=O)[CH2:19][C:20](=O)[C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:17][CH2:16]1>C1(C)C=CC=CC=1>[CH:15]1([C:18]2[CH:19]=[C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:6]3[C:2]([CH3:1])=[N:3][N:4]([CH:8]4[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]4)[C:5]=3[N:7]=2)[CH2:16][CH2:17]1 | Cc1cc(N)n(C2CCN(C)CC2)n1 | CCOC(=O)C(=O)CC(=O)C1CC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Cc1ccccc1 | null | null | null | null | null | null | null | null | null | null | 70 | null | 3-Methyl-1-(1-methyl-4-piperidinyl)-1H-pyrazol-5-amine (500 mg, 2.57 mmol) and ethyl 4-cyclopropyl-2,4-dioxobutanoate (474 mg, 2.57 mmol) were suspended in Toluene (10 mL) and heated at 70° C. for 5 h. The solvent was removed in vacuo and the crude residue was purified via silica gel chromatography (eluent: gradient of 0 to 10% MeOH:DCM). The final product was collected as a solid, 0.722 g (76%). LCMS E-S (M+H)=343.1 1H NMR (400 MHz, DMSO-d6) δ ppm 1.03-1.11 (m, 4H), 1.38 (t, J=7.07 Hz, 3H), 1.83 (d, J=6.06 Hz, 2H), 2.12-2.22 (m, 4H), 2.27 (s, 3H), 2.35 (m, J=7.83, 7.83, 5.05, 4.80 Hz, 1H), 2.54 (s, 3H), 2.94 (d, J=6.57 Hz, 2H), 4.42 (q, J=7.16 Hz, 2H), 4.57-4.73 (m, 1H), 7.46 (s, 1H). | CCOC(=O)c1cc(C2CC2)nc2c1c(C)nn2C1CCN(C)CC1 | null | null | null |
922,226 | ord_dataset-8e59bd24817446f7b1c68e805b8e5f1d | null | 2009-01-01T00:11:00 | true | [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:17](=[O:18])[C:16]2[C@H:15]3[C:19]([CH3:21])([CH3:20])[C@:12]([CH3:22])([CH2:13][CH2:14]3)[C:11]=2[NH:10]1.I[CH2:24][CH2:25][CH:26]([CH3:28])[CH3:27]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:17](=[O:18])[C:16]2[C@H:15]3[C:19]([CH3:21])([CH3:20])[C@:12]([CH3:22])([CH2:13][CH2:14]3)[C:11]=2[N:10]1[CH2:24][CH2:25][CH:26]([CH3:28])[CH3:27] | CC1(C)[C@H]2CC[C@]1(C)c1[nH]n(-c3ccc(F)cc3Cl)c(=O)c12 | CC(C)CCI | null | CCCC[N+](CCCC)(CCCC)CCCC | [I-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CN(C)C=O | null | null | null | null | null | null | null | null | null | null | 80 | null | A mixture of (4R,7S)-2-(2-chloro-4-fluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 43; 150 mg, 0.47 mmol), tetrabutylammonium iodide (174 mg, 0.47 mmol) and 1-iodo-3-methylbutane (230 μL, 1.75 mmol) in dimethylformamide (3 mL) was heated at 80° C. for 4 days. The solvent was evaporated and dichloromethane (50 mL) was added. The solution was washed with water (2×20 mL), saturated aqueous sodium thiosulfate (20 mL), and brine (20 mL), dried (magnesium sulfate), filtered, concentrated, purified by chromatography, eluting with 60-80% ethyl acetate/petroleum ether, and dried under high vacuum overnight to give (4R,7S)-2-(2-chloro-4-fluoro-phenyl)-7,8,8-trimethyl-1-(3-methyl-butyl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (31 mg, 17%) as a tacky oil. APCI(+)-MS (M+H) 391. | CC(C)CCn1c2c(c(=O)n1-c1ccc(F)cc1Cl)[C@@H]1CC[C@@]2(C)C1(C)C | null | 16.9 | null |
842,883 | ord_dataset-e2b35e721c2741999b0005d12691f9fe | null | 2008-01-01T00:10:00 | true | FC(F)(F)C(O)=O.[CH3:8][O:9][C:10](=[O:32])[C:11]1[CH:16]=[C:15]([O:17]COC)[CH:14]=[C:13]([O:21][C:22]2[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:24][CH:23]=2)[CH:12]=1>C(Cl)Cl>[CH3:8][O:9][C:10](=[O:32])[C:11]1[CH:16]=[C:15]([OH:17])[CH:14]=[C:13]([O:21][C:22]2[CH:23]=[CH:24][C:25]([S:28]([CH3:31])(=[O:29])=[O:30])=[CH:26][CH:27]=2)[CH:12]=1 | COCOc1cc(Oc2ccc(S(C)(=O)=O)cc2)cc(C(=O)OC)c1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | ClCCl | O=C(O)C(F)(F)F | null | null | null | null | null | null | null | null | null | 25 | 4 | After adding 60 ml of trifluoroacetic acid to a solution of 30.9 g (84.3 mmol) of the obtained 3-(4-methanesulfonyl-phenoxy)-5-methoxymethoxy-benzoic acid methyl ester in methylene chloride (100 ml) while cooling on ice, the reaction mixture was stirred at room temperature for 4 hours. The reaction mixture was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane:acetic acid ethyl ester=1:1) to obtain 15.2 g of 5-hydroxy-3-(4-methanesulfonyl-phenoxy)benzoic acid methyl ester (yield: 56%) as a white solid. | COC(=O)c1cc(O)cc(Oc2ccc(S(C)(=O)=O)cc2)c1 | null | 55.9 | null |
1,035,407 | ord_dataset-3af92aec23dc4810b92eb0d8c60023ee | null | 2011-01-01T00:03:00 | true | [CH:1]1[C:10]2[C:5](=[CH:6][C:7]([CH:11]=O)=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.Cl.[NH2:14][OH:15].[OH-].[Na+].Cl>CCO.O>[CH:1]1[C:10]2[C:5](=[CH:6][C:7](/[CH:11]=[N:14]/[OH:15])=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1 | O=Cc1ccc2cnccc2c1 | NO | null | Cl | [Na+] | [OH-] | null | null | null | null | null | null | null | null | null | null | null | null | null | null | O | CCO | null | null | null | null | null | null | null | null | null | 0 | 2 | To a solution of isoquinoline-6-carbaldehyde (2.48 g, 15.8 mmol) (prepared as shown in Example 6) in 160 mL of 1:2 EtOH:H2O was added hydroxylamine hydrochloride (1.21 g, 17.4 mmol). The mixture was cooled to 0° C., and 50 wt % NaOH in H2O (3.2 mL, 0.2 mL per mmol of aldehyde) was added dropwise. The mixture was then stirred at 0° C. for 2 hours, at which time the pH was adjusted to about 6 with 10% aqueous HCl. The resulting biphasic mixture was then transferred to a separatory funnel and extracted five times with 150 mL of DCM. The combined organic layers were dried over MgSO4. Concentration under reduced pressure afforded (E)-isoquinoline-6-carbaldehyde oxime (2.14 g, 78.8% yield) as a white solid. 1H NMR (400 MHz, CD3OD) δ ppm 9.20 (s, 1H), 8.44 (d, J=5.9 Hz, 1H), 8.28 (s, 1H), 8.06 (s, 2H), 7.99 (s, 1H), 7.83 (s, 5.9 Hz, 1H). | O/N=C/c1ccc2cnccc2c1 | null | 78.7 | null |
336,871 | ord_dataset-65c44df6676d4ce3a1874db5d7958ca9 | null | 1996-01-01T00:08:00 | true | Cl[CH2:2][CH2:3][C:4]1[C:5](=[O:23])[O:6][C:7]2[CH:14]=[C:13]([O:15][CH2:16][CH2:17][CH3:18])[CH:12]=[C:11]([O:19][CH2:20][CH2:21][CH3:22])[C:8]=2[C:9]=1[CH3:10].[CH3:24][O:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1>>[CH3:24][O:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[N:32]1[CH2:37][CH2:36][N:35]([CH2:2][CH2:3][C:4]2[C:5](=[O:23])[O:6][C:7]3[CH:14]=[C:13]([O:15][CH2:16][CH2:17][CH3:18])[CH:12]=[C:11]([O:19][CH2:20][CH2:21][CH3:22])[C:8]=3[C:9]=2[CH3:10])[CH2:34][CH2:33]1 | CCCOc1cc(OCCC)c2c(C)c(CCCl)c(=O)oc2c1 | COc1ccccc1N1CCNCC1 | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | Process B; starting materials: 3-(2-chloroethyl)-4-methyl-5,7-dipropoxy-2H-1-benzopyran-2-one (Example 38) and 1-(2-methoxyphenyl)piperazine; yield 47% of crude product. | CCCOc1cc(OCCC)c2c(C)c(CCN3CCN(c4ccccc4OC)CC3)c(=O)oc2c1 | null | 47 | null |
603,479 | ord_dataset-273fda773e864aaf9b71a30a2d9f2162 | null | 2003-01-01T00:08:00 | true | [CH3:1]C(N(C)C)=O.[NH2:7][C:8]1[C:9]([OH:27])=[C:10]([N:16]2[C:21](=[O:22])[N:20]([CH3:23])[C:19](=[S:24])[N:18]([CH3:25])[C:17]2=[O:26])[C:11]([F:15])=[CH:12][C:13]=1[Cl:14]>CO>[Cl:14][C:13]1[C:8]2[N:7]=[CH:1][O:27][C:9]=2[C:10]([N:16]2[C:21](=[O:22])[N:20]([CH3:23])[C:19](=[S:24])[N:18]([CH3:25])[C:17]2=[O:26])=[C:11]([F:15])[CH:12]=1 | CC(=O)N(C)C | Cn1c(=S)n(C)c(=O)n(-c2c(F)cc(Cl)c(N)c2O)c1=O | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | null | CO | null | null | null | null | null | null | null | null | null | null | null | null | 5.0 g (48.1 mmol) of trimethylformamide were added dropwise to a solution of 502 mg (1.50 mmol) of 3-(3-amino-4-chloro-6-fluoro-2-hydroxyphenyl)-1,5-dimethyl-6-thioxo-[1,3,5]-triazinane-2,4-dione in 10 ml of methanol. The mixture was then heated at reflux temperature for 9 hours. The reaction mixture was subsequently concentrated under reduced pressure. The resulting crude product was purified by means of column chromatography (mobile phase: cyclohexane/ethyl acetate=20:1). Yield: 240 mg (46%); m.p.: 209-211° C. | Cn1c(=S)n(C)c(=O)n(-c2c(F)cc(Cl)c3ncoc23)c1=O | null | null | null |
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